#psychedelicresearch — Public Fediverse posts

DATE: September 5, 2026 at 10:00AM
SOURCE: PSYPOST.ORG

** Research quality varies widely from fantastic to small exploratory studies. Please check research methods when conclusions are very important to you. **
-------------------------------------------------

TITLE: First human trial of psilocin since the 1960s reveals better tolerability than psilocybin

URL: https://www.psypost.org/first-human-trial-of-psilocin-since-the-1960s-reveals-better-tolerability-than-psilocybin/

Recent research suggests that consuming psilocin, the active compound in “magic” mushrooms, might cause fewer side effects than taking psilocybin. The study also explored taking the drug under the tongue, finding it well tolerated though less intense at the tested doses. The findings were published in Journal of Psychopharmacology.

Psilocybin is a naturally occurring compound found in certain hallucinogenic mushrooms. In recent years, it has gained attention as a potential treatment for mental health conditions. For example, a study covered by PsyPost in 2021 noted that psilocybin therapy could offer symptom relief comparable to some conventional antidepressants.

However, psilocybin itself does not directly cause psychedelic effects. It is a prodrug, meaning the body must break it down to activate it. When a person swallows psilocybin, enzymes in the gut and liver strip away a phosphate molecule, converting it into a new chemical called psilocin.

Psilocin is the active substance that enters the brain and alters perception. In fact, a 2019 study indicated that the intensity of a person’s psychedelic experience closely matches the concentration of psilocin circulating in their blood. Because the body’s conversion process can vary from person to person, standard oral psilocybin often yields unpredictable results and tends to cause unpleasant side effects.

“Nearly every modern psilocybin trial has used the same thing: synthetic psilocybin, 25 mg, in a capsule,” Josh Woolley, an associate professor of psychiatry at the University of California, San Francisco and director of the Translational Psychedelic Research Program, told PsyPost. “There are reasons to think other options might work better. Psilocybin is a prodrug, so the body has to convert it to psilocin, and people vary a lot in how efficiently they do that. That may be part of why responses to a fixed dose are so variable.”

Researchers wanted to know if administering psilocin directly would skip this metabolic step, potentially offering a gentler and more predictable experience. They also wanted to test a sublingual route, which involves placing a dissolving tablet under the tongue. Sublingual administration allows a drug to absorb directly into the bloodstream through the tissues of the mouth, completely bypassing the digestive system.

“Nobody had given psilocin directly to a human since the 1960s, and nobody had tried a sublingual formulation of any of these compounds,” Woolley noted.

Additionally, the research team used botanical extracts rather than lab-made synthetic chemicals. These whole-mushroom formulations contain natural trace compounds, known as alkaloids, alongside the primary drug. Alkaloids are naturally occurring chemical compounds found in plants and fungi that produce physiological effects on the body, and some researchers suspect they might influence the overall experience. “Mushrooms contain other alkaloids besides psilocybin, and standardized botanical extracts now make it possible to test whole-mushroom formulations under pharmaceutical conditions, which hadn’t been done,” Woolley said.

The research, led by Marlene L. Tai and Woolley, aimed to compare these different methods in a controlled setting. The scientists recruited 20 healthy adults between the ages of 25 and 50. All participants had prior experience with psychedelics and reported mild feelings of social disconnection. The study used a crossover design, meaning each person received multiple different treatments on separate days to compare the effects within the same individual.

Participants attended up to four drug administration sessions spaced four weeks apart. During these sessions, they received either an oral capsule of psilocybin (25 milligrams), an oral capsule of psilocin (17.5 milligrams, a dose designed to match the psilocybin strength), or a sublingual tablet of psilocin. The initial sublingual dose was set low at 2.18 milligrams and later increased to 4.36 milligrams or 8 milligrams to assess safety and tolerability.

All sessions took place in a comfortable clinic room where participants wore eyeshades and listened to music. A therapist and an assistant stayed in the room to provide psychological support. Throughout the day, the research team measured blood pressure and heart rate, while participants rated the intensity of the drug’s effects every 15 to 30 minutes.

At the end of each session, participants completed several questionnaires. These surveys measured the emotional and psychological qualities of their experience, including feelings of unity, emotional breakthroughs, and challenging states like fear or paranoia.

When comparing the two oral capsules, the scientists found that psilocin produced a psychological and physical journey that was very similar to psilocybin. The onset time, peak intensity, and duration of the experiences were mostly indistinguishable. Both drugs reliably produced deep psychological insights and mystical-type experiences.

“We expected psilocin to come on faster, since it skips a metabolic step, and it didn’t,” Woolley explained. “The two were hard to tell apart on almost every measure.”

However, oral psilocin was associated with a lower overall burden of adverse side effects. While almost all participants experienced mild issues on both drugs, oral psilocybin was linked to more moderate and severe events. These included headaches, anxiety, and one instance of transient loss of consciousness. Interestingly, gastrointestinal issues like nausea were similar between the two oral drugs, suggesting that stomach upset is not solely caused by the body breaking down psilocybin.

“The tolerability difference was modest, not dramatic,” Woolley said. “Fewer and milder adverse events on average, mostly headache and anxiety, rather than a categorical improvement. Whether that matters clinically depends on the setting. In a treatment where one session already requires eight hours of monitoring, small reductions in burden can add up. But this was 18 people per condition, so it’s a signal worth following, not an established difference.”

The sublingual psilocin tablets proved safe and were well tolerated by the participants. But the physical and psychological effects were much milder than the oral doses. The subjective intensity and cardiovascular responses were noticeably lower, indicating that less of the drug made its way into the systemic circulation at the tested amounts.

“At the cautious doses we used with FDA input, we clearly didn’t reach the exposure needed to test whether the route has real advantages,” Woolley noted. “This is an early study in 20 healthy volunteers. It’s a first look, not a verdict.”

Despite the milder overall intensity, sublingual psilocin still facilitated notable psychological responses. Participants reported scores on measures of emotional breakthrough and psychological insight that rivaled those typically seen with much higher oral doses. The authors noted that this suggests even mild psychedelic exposures might offer some therapeutic benefit.

“One result we’re still thinking about,” the researcher stated. “Even the very mild sublingual doses produced emotional breakthrough scores comparable to the full 25 mg doses. That could be a false positive, or an effect of the psychotherapy rather than the drug. But if it holds, it raises a real question about whether an intense psychedelic experience is necessary for the psychological benefits people are after.”

In an exploratory analysis, the researchers also compared their botanical mushroom extracts to data from a separate trial that used synthetic psilocybin. The psychological effects were broadly similar. This provides evidence that standardized whole-mushroom extracts function much like lab-made versions, offering a viable alternative for future treatments.

“On the botanical question, our comparison was with data from a previously published trial of synthetic psilocybin, not with a synthetic arm in our own study,” Woolley explained. “Two different populations, two different settings. So the fair statement is that we saw nothing that would suggest a big difference, not that we ruled one out. Testing the ‘entourage effect’ properly would require a head-to-head comparison in the same trial.” This entourage effect is the theory that multiple natural compounds within a plant or mushroom work together synergistically to produce stronger or different effects than an isolated chemical alone.

As with all research, there are a few things to keep in mind. The study included a small group of healthy, highly educated volunteers who already had experience with psychedelics. Because of this, it is not guaranteed that people with severe mental health conditions or those entirely new to psychedelics would respond in the exact same way.

The researchers also emphasized the strict clinical environment used during the trial. “The main one is that nothing here suggests people should be taking mushroom extracts on their own or trying to convert psilocybin to psilocin at home,” Woolley warned. “These were pharmaceutical grade products made to Good Manufacturing Practice standards, given under continuous medical supervision with a licensed therapist present throughout. That matters. One participant briefly lost consciousness during a psilocybin session, which we’ve reported separately, and it was handled because clinicians were in the room.”

The trial also lacked a pure inactive placebo group. Because the sublingual doses produced noticeably milder physical sensations than the oral capsules, participants and therapists were often able to guess which treatment had been administered. This awareness could have influenced the subjective survey responses.

Finally, the research team did not collect blood samples during the sessions. Without measuring the actual concentration of psilocin in the blood, it is difficult to know exactly how much of the sublingual drug was absorbed or how individual metabolisms processed the oral capsules. Future studies will need to incorporate blood testing and try higher sublingual doses to fully evaluate this delivery method.

“Measuring actual psilocin levels is what would let us link formulation to exposure to effect, and its absence was our main limitation here,” Woolley observed. “Sublingual psilocin needs a proper dose-ranging study at higher doses. And eventually this has to be tested in people with the conditions these drugs might treat, not just healthy volunteers.”

Moving forward, the team intends to share additional findings from the current participants. “We have a companion paper in preparation from this same trial looking at longer-term psychological outcomes, including loneliness, out to six months,” Woolley, who also serves as a staff psychiatrist at the San Francisco VA Medical Center, added. “That’s the other half of the story and we’ll have more to say when it’s out.”

The study, “A randomized crossover trial comparing the acute physiological and psychological effects of botanical formulations of oral psilocybin, oral psilocin, and sublingual psilocin,” was authored by Marlene L. Tai, Balázs Szigeti, Amanda E. Downey, Jacob S. Aday, Lisa Fredenburg, Kimberly Sakai, Cesar Molina, Gisele Fernandes-Osterhold, Ellen R. Bradley, Maddie Pantoni, Ryan Moss, Benjamin Lightburn, Franziska Plessow, Aoife O’Donovan, and Josh D. Woolley.

URL: https://www.psypost.org/first-human-trial-of-psilocin-since-the-1960s-reveals-better-tolerability-than-psilocybin/

-------------------------------------------------

Private, vetted email list for mental health professionals: https://www.clinicians-exchange.org

Unofficial Psychology Today Xitter to toot feed at Psych Today Unofficial Bot @PTUnofficialBot

-------------------------------------------------

#psychology #counseling #socialwork #psychotherapy @psychotherapist @psychotherapists @psychology @socialpsych @socialwork @psychiatry #mentalhealth #psychiatry #healthcare #depression #psychotherapist #psilocin #psilocybin #psychedelicresearch #mentalhealth #sublingual #botanicalextracts #psychopharmacology #entourageeffect #clinicaltrial #psychedelics

DATE: September 5, 2026 at 10:00AM
SOURCE: PSYPOST.ORG

** Research quality varies widely from fantastic to small exploratory studies. Please check research methods when conclusions are very important to you. **
-------------------------------------------------

TITLE: First human trial of psilocin since the 1960s reveals better tolerability than psilocybin

URL: https://www.psypost.org/first-human-trial-of-psilocin-since-the-1960s-reveals-better-tolerability-than-psilocybin/

Recent research suggests that consuming psilocin, the active compound in “magic” mushrooms, might cause fewer side effects than taking psilocybin. The study also explored taking the drug under the tongue, finding it well tolerated though less intense at the tested doses. The findings were published in Journal of Psychopharmacology.

Psilocybin is a naturally occurring compound found in certain hallucinogenic mushrooms. In recent years, it has gained attention as a potential treatment for mental health conditions. For example, a study covered by PsyPost in 2021 noted that psilocybin therapy could offer symptom relief comparable to some conventional antidepressants.

However, psilocybin itself does not directly cause psychedelic effects. It is a prodrug, meaning the body must break it down to activate it. When a person swallows psilocybin, enzymes in the gut and liver strip away a phosphate molecule, converting it into a new chemical called psilocin.

Psilocin is the active substance that enters the brain and alters perception. In fact, a 2019 study indicated that the intensity of a person’s psychedelic experience closely matches the concentration of psilocin circulating in their blood. Because the body’s conversion process can vary from person to person, standard oral psilocybin often yields unpredictable results and tends to cause unpleasant side effects.

“Nearly every modern psilocybin trial has used the same thing: synthetic psilocybin, 25 mg, in a capsule,” Josh Woolley, an associate professor of psychiatry at the University of California, San Francisco and director of the Translational Psychedelic Research Program, told PsyPost. “There are reasons to think other options might work better. Psilocybin is a prodrug, so the body has to convert it to psilocin, and people vary a lot in how efficiently they do that. That may be part of why responses to a fixed dose are so variable.”

Researchers wanted to know if administering psilocin directly would skip this metabolic step, potentially offering a gentler and more predictable experience. They also wanted to test a sublingual route, which involves placing a dissolving tablet under the tongue. Sublingual administration allows a drug to absorb directly into the bloodstream through the tissues of the mouth, completely bypassing the digestive system.

“Nobody had given psilocin directly to a human since the 1960s, and nobody had tried a sublingual formulation of any of these compounds,” Woolley noted.

Additionally, the research team used botanical extracts rather than lab-made synthetic chemicals. These whole-mushroom formulations contain natural trace compounds, known as alkaloids, alongside the primary drug. Alkaloids are naturally occurring chemical compounds found in plants and fungi that produce physiological effects on the body, and some researchers suspect they might influence the overall experience. “Mushrooms contain other alkaloids besides psilocybin, and standardized botanical extracts now make it possible to test whole-mushroom formulations under pharmaceutical conditions, which hadn’t been done,” Woolley said.

The research, led by Marlene L. Tai and Woolley, aimed to compare these different methods in a controlled setting. The scientists recruited 20 healthy adults between the ages of 25 and 50. All participants had prior experience with psychedelics and reported mild feelings of social disconnection. The study used a crossover design, meaning each person received multiple different treatments on separate days to compare the effects within the same individual.

Participants attended up to four drug administration sessions spaced four weeks apart. During these sessions, they received either an oral capsule of psilocybin (25 milligrams), an oral capsule of psilocin (17.5 milligrams, a dose designed to match the psilocybin strength), or a sublingual tablet of psilocin. The initial sublingual dose was set low at 2.18 milligrams and later increased to 4.36 milligrams or 8 milligrams to assess safety and tolerability.

All sessions took place in a comfortable clinic room where participants wore eyeshades and listened to music. A therapist and an assistant stayed in the room to provide psychological support. Throughout the day, the research team measured blood pressure and heart rate, while participants rated the intensity of the drug’s effects every 15 to 30 minutes.

At the end of each session, participants completed several questionnaires. These surveys measured the emotional and psychological qualities of their experience, including feelings of unity, emotional breakthroughs, and challenging states like fear or paranoia.

When comparing the two oral capsules, the scientists found that psilocin produced a psychological and physical journey that was very similar to psilocybin. The onset time, peak intensity, and duration of the experiences were mostly indistinguishable. Both drugs reliably produced deep psychological insights and mystical-type experiences.

“We expected psilocin to come on faster, since it skips a metabolic step, and it didn’t,” Woolley explained. “The two were hard to tell apart on almost every measure.”

However, oral psilocin was associated with a lower overall burden of adverse side effects. While almost all participants experienced mild issues on both drugs, oral psilocybin was linked to more moderate and severe events. These included headaches, anxiety, and one instance of transient loss of consciousness. Interestingly, gastrointestinal issues like nausea were similar between the two oral drugs, suggesting that stomach upset is not solely caused by the body breaking down psilocybin.

“The tolerability difference was modest, not dramatic,” Woolley said. “Fewer and milder adverse events on average, mostly headache and anxiety, rather than a categorical improvement. Whether that matters clinically depends on the setting. In a treatment where one session already requires eight hours of monitoring, small reductions in burden can add up. But this was 18 people per condition, so it’s a signal worth following, not an established difference.”

The sublingual psilocin tablets proved safe and were well tolerated by the participants. But the physical and psychological effects were much milder than the oral doses. The subjective intensity and cardiovascular responses were noticeably lower, indicating that less of the drug made its way into the systemic circulation at the tested amounts.

“At the cautious doses we used with FDA input, we clearly didn’t reach the exposure needed to test whether the route has real advantages,” Woolley noted. “This is an early study in 20 healthy volunteers. It’s a first look, not a verdict.”

Despite the milder overall intensity, sublingual psilocin still facilitated notable psychological responses. Participants reported scores on measures of emotional breakthrough and psychological insight that rivaled those typically seen with much higher oral doses. The authors noted that this suggests even mild psychedelic exposures might offer some therapeutic benefit.

“One result we’re still thinking about,” the researcher stated. “Even the very mild sublingual doses produced emotional breakthrough scores comparable to the full 25 mg doses. That could be a false positive, or an effect of the psychotherapy rather than the drug. But if it holds, it raises a real question about whether an intense psychedelic experience is necessary for the psychological benefits people are after.”

In an exploratory analysis, the researchers also compared their botanical mushroom extracts to data from a separate trial that used synthetic psilocybin. The psychological effects were broadly similar. This provides evidence that standardized whole-mushroom extracts function much like lab-made versions, offering a viable alternative for future treatments.

“On the botanical question, our comparison was with data from a previously published trial of synthetic psilocybin, not with a synthetic arm in our own study,” Woolley explained. “Two different populations, two different settings. So the fair statement is that we saw nothing that would suggest a big difference, not that we ruled one out. Testing the ‘entourage effect’ properly would require a head-to-head comparison in the same trial.” This entourage effect is the theory that multiple natural compounds within a plant or mushroom work together synergistically to produce stronger or different effects than an isolated chemical alone.

As with all research, there are a few things to keep in mind. The study included a small group of healthy, highly educated volunteers who already had experience with psychedelics. Because of this, it is not guaranteed that people with severe mental health conditions or those entirely new to psychedelics would respond in the exact same way.

The researchers also emphasized the strict clinical environment used during the trial. “The main one is that nothing here suggests people should be taking mushroom extracts on their own or trying to convert psilocybin to psilocin at home,” Woolley warned. “These were pharmaceutical grade products made to Good Manufacturing Practice standards, given under continuous medical supervision with a licensed therapist present throughout. That matters. One participant briefly lost consciousness during a psilocybin session, which we’ve reported separately, and it was handled because clinicians were in the room.”

The trial also lacked a pure inactive placebo group. Because the sublingual doses produced noticeably milder physical sensations than the oral capsules, participants and therapists were often able to guess which treatment had been administered. This awareness could have influenced the subjective survey responses.

Finally, the research team did not collect blood samples during the sessions. Without measuring the actual concentration of psilocin in the blood, it is difficult to know exactly how much of the sublingual drug was absorbed or how individual metabolisms processed the oral capsules. Future studies will need to incorporate blood testing and try higher sublingual doses to fully evaluate this delivery method.

“Measuring actual psilocin levels is what would let us link formulation to exposure to effect, and its absence was our main limitation here,” Woolley observed. “Sublingual psilocin needs a proper dose-ranging study at higher doses. And eventually this has to be tested in people with the conditions these drugs might treat, not just healthy volunteers.”

Moving forward, the team intends to share additional findings from the current participants. “We have a companion paper in preparation from this same trial looking at longer-term psychological outcomes, including loneliness, out to six months,” Woolley, who also serves as a staff psychiatrist at the San Francisco VA Medical Center, added. “That’s the other half of the story and we’ll have more to say when it’s out.”

The study, “A randomized crossover trial comparing the acute physiological and psychological effects of botanical formulations of oral psilocybin, oral psilocin, and sublingual psilocin,” was authored by Marlene L. Tai, Balázs Szigeti, Amanda E. Downey, Jacob S. Aday, Lisa Fredenburg, Kimberly Sakai, Cesar Molina, Gisele Fernandes-Osterhold, Ellen R. Bradley, Maddie Pantoni, Ryan Moss, Benjamin Lightburn, Franziska Plessow, Aoife O’Donovan, and Josh D. Woolley.

URL: https://www.psypost.org/first-human-trial-of-psilocin-since-the-1960s-reveals-better-tolerability-than-psilocybin/

-------------------------------------------------

Private, vetted email list for mental health professionals: https://www.clinicians-exchange.org

Unofficial Psychology Today Xitter to toot feed at Psych Today Unofficial Bot @PTUnofficialBot

-------------------------------------------------

#psychology #counseling #socialwork #psychotherapy @psychotherapist @psychotherapists @psychology @socialpsych @socialwork @psychiatry #mentalhealth #psychiatry #healthcare #depression #psychotherapist #psilocin #psilocybin #psychedelicresearch #mentalhealth #sublingual #botanicalextracts #psychopharmacology #entourageeffect #clinicaltrial #psychedelics

DATE: September 5, 2026 at 10:00AM
SOURCE: PSYPOST.ORG

** Research quality varies widely from fantastic to small exploratory studies. Please check research methods when conclusions are very important to you. **
-------------------------------------------------

TITLE: First human trial of psilocin since the 1960s reveals better tolerability than psilocybin

URL: https://www.psypost.org/first-human-trial-of-psilocin-since-the-1960s-reveals-better-tolerability-than-psilocybin/

Recent research suggests that consuming psilocin, the active compound in “magic” mushrooms, might cause fewer side effects than taking psilocybin. The study also explored taking the drug under the tongue, finding it well tolerated though less intense at the tested doses. The findings were published in Journal of Psychopharmacology.

Psilocybin is a naturally occurring compound found in certain hallucinogenic mushrooms. In recent years, it has gained attention as a potential treatment for mental health conditions. For example, a study covered by PsyPost in 2021 noted that psilocybin therapy could offer symptom relief comparable to some conventional antidepressants.

However, psilocybin itself does not directly cause psychedelic effects. It is a prodrug, meaning the body must break it down to activate it. When a person swallows psilocybin, enzymes in the gut and liver strip away a phosphate molecule, converting it into a new chemical called psilocin.

Psilocin is the active substance that enters the brain and alters perception. In fact, a 2019 study indicated that the intensity of a person’s psychedelic experience closely matches the concentration of psilocin circulating in their blood. Because the body’s conversion process can vary from person to person, standard oral psilocybin often yields unpredictable results and tends to cause unpleasant side effects.

“Nearly every modern psilocybin trial has used the same thing: synthetic psilocybin, 25 mg, in a capsule,” Josh Woolley, an associate professor of psychiatry at the University of California, San Francisco and director of the Translational Psychedelic Research Program, told PsyPost. “There are reasons to think other options might work better. Psilocybin is a prodrug, so the body has to convert it to psilocin, and people vary a lot in how efficiently they do that. That may be part of why responses to a fixed dose are so variable.”

Researchers wanted to know if administering psilocin directly would skip this metabolic step, potentially offering a gentler and more predictable experience. They also wanted to test a sublingual route, which involves placing a dissolving tablet under the tongue. Sublingual administration allows a drug to absorb directly into the bloodstream through the tissues of the mouth, completely bypassing the digestive system.

“Nobody had given psilocin directly to a human since the 1960s, and nobody had tried a sublingual formulation of any of these compounds,” Woolley noted.

Additionally, the research team used botanical extracts rather than lab-made synthetic chemicals. These whole-mushroom formulations contain natural trace compounds, known as alkaloids, alongside the primary drug. Alkaloids are naturally occurring chemical compounds found in plants and fungi that produce physiological effects on the body, and some researchers suspect they might influence the overall experience. “Mushrooms contain other alkaloids besides psilocybin, and standardized botanical extracts now make it possible to test whole-mushroom formulations under pharmaceutical conditions, which hadn’t been done,” Woolley said.

The research, led by Marlene L. Tai and Woolley, aimed to compare these different methods in a controlled setting. The scientists recruited 20 healthy adults between the ages of 25 and 50. All participants had prior experience with psychedelics and reported mild feelings of social disconnection. The study used a crossover design, meaning each person received multiple different treatments on separate days to compare the effects within the same individual.

Participants attended up to four drug administration sessions spaced four weeks apart. During these sessions, they received either an oral capsule of psilocybin (25 milligrams), an oral capsule of psilocin (17.5 milligrams, a dose designed to match the psilocybin strength), or a sublingual tablet of psilocin. The initial sublingual dose was set low at 2.18 milligrams and later increased to 4.36 milligrams or 8 milligrams to assess safety and tolerability.

All sessions took place in a comfortable clinic room where participants wore eyeshades and listened to music. A therapist and an assistant stayed in the room to provide psychological support. Throughout the day, the research team measured blood pressure and heart rate, while participants rated the intensity of the drug’s effects every 15 to 30 minutes.

At the end of each session, participants completed several questionnaires. These surveys measured the emotional and psychological qualities of their experience, including feelings of unity, emotional breakthroughs, and challenging states like fear or paranoia.

When comparing the two oral capsules, the scientists found that psilocin produced a psychological and physical journey that was very similar to psilocybin. The onset time, peak intensity, and duration of the experiences were mostly indistinguishable. Both drugs reliably produced deep psychological insights and mystical-type experiences.

“We expected psilocin to come on faster, since it skips a metabolic step, and it didn’t,” Woolley explained. “The two were hard to tell apart on almost every measure.”

However, oral psilocin was associated with a lower overall burden of adverse side effects. While almost all participants experienced mild issues on both drugs, oral psilocybin was linked to more moderate and severe events. These included headaches, anxiety, and one instance of transient loss of consciousness. Interestingly, gastrointestinal issues like nausea were similar between the two oral drugs, suggesting that stomach upset is not solely caused by the body breaking down psilocybin.

“The tolerability difference was modest, not dramatic,” Woolley said. “Fewer and milder adverse events on average, mostly headache and anxiety, rather than a categorical improvement. Whether that matters clinically depends on the setting. In a treatment where one session already requires eight hours of monitoring, small reductions in burden can add up. But this was 18 people per condition, so it’s a signal worth following, not an established difference.”

The sublingual psilocin tablets proved safe and were well tolerated by the participants. But the physical and psychological effects were much milder than the oral doses. The subjective intensity and cardiovascular responses were noticeably lower, indicating that less of the drug made its way into the systemic circulation at the tested amounts.

“At the cautious doses we used with FDA input, we clearly didn’t reach the exposure needed to test whether the route has real advantages,” Woolley noted. “This is an early study in 20 healthy volunteers. It’s a first look, not a verdict.”

Despite the milder overall intensity, sublingual psilocin still facilitated notable psychological responses. Participants reported scores on measures of emotional breakthrough and psychological insight that rivaled those typically seen with much higher oral doses. The authors noted that this suggests even mild psychedelic exposures might offer some therapeutic benefit.

“One result we’re still thinking about,” the researcher stated. “Even the very mild sublingual doses produced emotional breakthrough scores comparable to the full 25 mg doses. That could be a false positive, or an effect of the psychotherapy rather than the drug. But if it holds, it raises a real question about whether an intense psychedelic experience is necessary for the psychological benefits people are after.”

In an exploratory analysis, the researchers also compared their botanical mushroom extracts to data from a separate trial that used synthetic psilocybin. The psychological effects were broadly similar. This provides evidence that standardized whole-mushroom extracts function much like lab-made versions, offering a viable alternative for future treatments.

“On the botanical question, our comparison was with data from a previously published trial of synthetic psilocybin, not with a synthetic arm in our own study,” Woolley explained. “Two different populations, two different settings. So the fair statement is that we saw nothing that would suggest a big difference, not that we ruled one out. Testing the ‘entourage effect’ properly would require a head-to-head comparison in the same trial.” This entourage effect is the theory that multiple natural compounds within a plant or mushroom work together synergistically to produce stronger or different effects than an isolated chemical alone.

As with all research, there are a few things to keep in mind. The study included a small group of healthy, highly educated volunteers who already had experience with psychedelics. Because of this, it is not guaranteed that people with severe mental health conditions or those entirely new to psychedelics would respond in the exact same way.

The researchers also emphasized the strict clinical environment used during the trial. “The main one is that nothing here suggests people should be taking mushroom extracts on their own or trying to convert psilocybin to psilocin at home,” Woolley warned. “These were pharmaceutical grade products made to Good Manufacturing Practice standards, given under continuous medical supervision with a licensed therapist present throughout. That matters. One participant briefly lost consciousness during a psilocybin session, which we’ve reported separately, and it was handled because clinicians were in the room.”

The trial also lacked a pure inactive placebo group. Because the sublingual doses produced noticeably milder physical sensations than the oral capsules, participants and therapists were often able to guess which treatment had been administered. This awareness could have influenced the subjective survey responses.

Finally, the research team did not collect blood samples during the sessions. Without measuring the actual concentration of psilocin in the blood, it is difficult to know exactly how much of the sublingual drug was absorbed or how individual metabolisms processed the oral capsules. Future studies will need to incorporate blood testing and try higher sublingual doses to fully evaluate this delivery method.

“Measuring actual psilocin levels is what would let us link formulation to exposure to effect, and its absence was our main limitation here,” Woolley observed. “Sublingual psilocin needs a proper dose-ranging study at higher doses. And eventually this has to be tested in people with the conditions these drugs might treat, not just healthy volunteers.”

Moving forward, the team intends to share additional findings from the current participants. “We have a companion paper in preparation from this same trial looking at longer-term psychological outcomes, including loneliness, out to six months,” Woolley, who also serves as a staff psychiatrist at the San Francisco VA Medical Center, added. “That’s the other half of the story and we’ll have more to say when it’s out.”

The study, “A randomized crossover trial comparing the acute physiological and psychological effects of botanical formulations of oral psilocybin, oral psilocin, and sublingual psilocin,” was authored by Marlene L. Tai, Balázs Szigeti, Amanda E. Downey, Jacob S. Aday, Lisa Fredenburg, Kimberly Sakai, Cesar Molina, Gisele Fernandes-Osterhold, Ellen R. Bradley, Maddie Pantoni, Ryan Moss, Benjamin Lightburn, Franziska Plessow, Aoife O’Donovan, and Josh D. Woolley.

URL: https://www.psypost.org/first-human-trial-of-psilocin-since-the-1960s-reveals-better-tolerability-than-psilocybin/

-------------------------------------------------

Private, vetted email list for mental health professionals: https://www.clinicians-exchange.org

Unofficial Psychology Today Xitter to toot feed at Psych Today Unofficial Bot @PTUnofficialBot

-------------------------------------------------

#psychology #counseling #socialwork #psychotherapy @psychotherapist @psychotherapists @psychology @socialpsych @socialwork @psychiatry #mentalhealth #psychiatry #healthcare #depression #psychotherapist #psilocin #psilocybin #psychedelicresearch #mentalhealth #sublingual #botanicalextracts #psychopharmacology #entourageeffect #clinicaltrial #psychedelics

DATE: September 5, 2026 at 10:00AM
SOURCE: PSYPOST.ORG

** Research quality varies widely from fantastic to small exploratory studies. Please check research methods when conclusions are very important to you. **
-------------------------------------------------

TITLE: First human trial of psilocin since the 1960s reveals better tolerability than psilocybin

URL: https://www.psypost.org/first-human-trial-of-psilocin-since-the-1960s-reveals-better-tolerability-than-psilocybin/

Recent research suggests that consuming psilocin, the active compound in “magic” mushrooms, might cause fewer side effects than taking psilocybin. The study also explored taking the drug under the tongue, finding it well tolerated though less intense at the tested doses. The findings were published in Journal of Psychopharmacology.

Psilocybin is a naturally occurring compound found in certain hallucinogenic mushrooms. In recent years, it has gained attention as a potential treatment for mental health conditions. For example, a study covered by PsyPost in 2021 noted that psilocybin therapy could offer symptom relief comparable to some conventional antidepressants.

However, psilocybin itself does not directly cause psychedelic effects. It is a prodrug, meaning the body must break it down to activate it. When a person swallows psilocybin, enzymes in the gut and liver strip away a phosphate molecule, converting it into a new chemical called psilocin.

Psilocin is the active substance that enters the brain and alters perception. In fact, a 2019 study indicated that the intensity of a person’s psychedelic experience closely matches the concentration of psilocin circulating in their blood. Because the body’s conversion process can vary from person to person, standard oral psilocybin often yields unpredictable results and tends to cause unpleasant side effects.

“Nearly every modern psilocybin trial has used the same thing: synthetic psilocybin, 25 mg, in a capsule,” Josh Woolley, an associate professor of psychiatry at the University of California, San Francisco and director of the Translational Psychedelic Research Program, told PsyPost. “There are reasons to think other options might work better. Psilocybin is a prodrug, so the body has to convert it to psilocin, and people vary a lot in how efficiently they do that. That may be part of why responses to a fixed dose are so variable.”

Researchers wanted to know if administering psilocin directly would skip this metabolic step, potentially offering a gentler and more predictable experience. They also wanted to test a sublingual route, which involves placing a dissolving tablet under the tongue. Sublingual administration allows a drug to absorb directly into the bloodstream through the tissues of the mouth, completely bypassing the digestive system.

“Nobody had given psilocin directly to a human since the 1960s, and nobody had tried a sublingual formulation of any of these compounds,” Woolley noted.

Additionally, the research team used botanical extracts rather than lab-made synthetic chemicals. These whole-mushroom formulations contain natural trace compounds, known as alkaloids, alongside the primary drug. Alkaloids are naturally occurring chemical compounds found in plants and fungi that produce physiological effects on the body, and some researchers suspect they might influence the overall experience. “Mushrooms contain other alkaloids besides psilocybin, and standardized botanical extracts now make it possible to test whole-mushroom formulations under pharmaceutical conditions, which hadn’t been done,” Woolley said.

The research, led by Marlene L. Tai and Woolley, aimed to compare these different methods in a controlled setting. The scientists recruited 20 healthy adults between the ages of 25 and 50. All participants had prior experience with psychedelics and reported mild feelings of social disconnection. The study used a crossover design, meaning each person received multiple different treatments on separate days to compare the effects within the same individual.

Participants attended up to four drug administration sessions spaced four weeks apart. During these sessions, they received either an oral capsule of psilocybin (25 milligrams), an oral capsule of psilocin (17.5 milligrams, a dose designed to match the psilocybin strength), or a sublingual tablet of psilocin. The initial sublingual dose was set low at 2.18 milligrams and later increased to 4.36 milligrams or 8 milligrams to assess safety and tolerability.

All sessions took place in a comfortable clinic room where participants wore eyeshades and listened to music. A therapist and an assistant stayed in the room to provide psychological support. Throughout the day, the research team measured blood pressure and heart rate, while participants rated the intensity of the drug’s effects every 15 to 30 minutes.

At the end of each session, participants completed several questionnaires. These surveys measured the emotional and psychological qualities of their experience, including feelings of unity, emotional breakthroughs, and challenging states like fear or paranoia.

When comparing the two oral capsules, the scientists found that psilocin produced a psychological and physical journey that was very similar to psilocybin. The onset time, peak intensity, and duration of the experiences were mostly indistinguishable. Both drugs reliably produced deep psychological insights and mystical-type experiences.

“We expected psilocin to come on faster, since it skips a metabolic step, and it didn’t,” Woolley explained. “The two were hard to tell apart on almost every measure.”

However, oral psilocin was associated with a lower overall burden of adverse side effects. While almost all participants experienced mild issues on both drugs, oral psilocybin was linked to more moderate and severe events. These included headaches, anxiety, and one instance of transient loss of consciousness. Interestingly, gastrointestinal issues like nausea were similar between the two oral drugs, suggesting that stomach upset is not solely caused by the body breaking down psilocybin.

“The tolerability difference was modest, not dramatic,” Woolley said. “Fewer and milder adverse events on average, mostly headache and anxiety, rather than a categorical improvement. Whether that matters clinically depends on the setting. In a treatment where one session already requires eight hours of monitoring, small reductions in burden can add up. But this was 18 people per condition, so it’s a signal worth following, not an established difference.”

The sublingual psilocin tablets proved safe and were well tolerated by the participants. But the physical and psychological effects were much milder than the oral doses. The subjective intensity and cardiovascular responses were noticeably lower, indicating that less of the drug made its way into the systemic circulation at the tested amounts.

“At the cautious doses we used with FDA input, we clearly didn’t reach the exposure needed to test whether the route has real advantages,” Woolley noted. “This is an early study in 20 healthy volunteers. It’s a first look, not a verdict.”

Despite the milder overall intensity, sublingual psilocin still facilitated notable psychological responses. Participants reported scores on measures of emotional breakthrough and psychological insight that rivaled those typically seen with much higher oral doses. The authors noted that this suggests even mild psychedelic exposures might offer some therapeutic benefit.

“One result we’re still thinking about,” the researcher stated. “Even the very mild sublingual doses produced emotional breakthrough scores comparable to the full 25 mg doses. That could be a false positive, or an effect of the psychotherapy rather than the drug. But if it holds, it raises a real question about whether an intense psychedelic experience is necessary for the psychological benefits people are after.”

In an exploratory analysis, the researchers also compared their botanical mushroom extracts to data from a separate trial that used synthetic psilocybin. The psychological effects were broadly similar. This provides evidence that standardized whole-mushroom extracts function much like lab-made versions, offering a viable alternative for future treatments.

“On the botanical question, our comparison was with data from a previously published trial of synthetic psilocybin, not with a synthetic arm in our own study,” Woolley explained. “Two different populations, two different settings. So the fair statement is that we saw nothing that would suggest a big difference, not that we ruled one out. Testing the ‘entourage effect’ properly would require a head-to-head comparison in the same trial.” This entourage effect is the theory that multiple natural compounds within a plant or mushroom work together synergistically to produce stronger or different effects than an isolated chemical alone.

As with all research, there are a few things to keep in mind. The study included a small group of healthy, highly educated volunteers who already had experience with psychedelics. Because of this, it is not guaranteed that people with severe mental health conditions or those entirely new to psychedelics would respond in the exact same way.

The researchers also emphasized the strict clinical environment used during the trial. “The main one is that nothing here suggests people should be taking mushroom extracts on their own or trying to convert psilocybin to psilocin at home,” Woolley warned. “These were pharmaceutical grade products made to Good Manufacturing Practice standards, given under continuous medical supervision with a licensed therapist present throughout. That matters. One participant briefly lost consciousness during a psilocybin session, which we’ve reported separately, and it was handled because clinicians were in the room.”

The trial also lacked a pure inactive placebo group. Because the sublingual doses produced noticeably milder physical sensations than the oral capsules, participants and therapists were often able to guess which treatment had been administered. This awareness could have influenced the subjective survey responses.

Finally, the research team did not collect blood samples during the sessions. Without measuring the actual concentration of psilocin in the blood, it is difficult to know exactly how much of the sublingual drug was absorbed or how individual metabolisms processed the oral capsules. Future studies will need to incorporate blood testing and try higher sublingual doses to fully evaluate this delivery method.

“Measuring actual psilocin levels is what would let us link formulation to exposure to effect, and its absence was our main limitation here,” Woolley observed. “Sublingual psilocin needs a proper dose-ranging study at higher doses. And eventually this has to be tested in people with the conditions these drugs might treat, not just healthy volunteers.”

Moving forward, the team intends to share additional findings from the current participants. “We have a companion paper in preparation from this same trial looking at longer-term psychological outcomes, including loneliness, out to six months,” Woolley, who also serves as a staff psychiatrist at the San Francisco VA Medical Center, added. “That’s the other half of the story and we’ll have more to say when it’s out.”

The study, “A randomized crossover trial comparing the acute physiological and psychological effects of botanical formulations of oral psilocybin, oral psilocin, and sublingual psilocin,” was authored by Marlene L. Tai, Balázs Szigeti, Amanda E. Downey, Jacob S. Aday, Lisa Fredenburg, Kimberly Sakai, Cesar Molina, Gisele Fernandes-Osterhold, Ellen R. Bradley, Maddie Pantoni, Ryan Moss, Benjamin Lightburn, Franziska Plessow, Aoife O’Donovan, and Josh D. Woolley.

URL: https://www.psypost.org/first-human-trial-of-psilocin-since-the-1960s-reveals-better-tolerability-than-psilocybin/

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DATE: September 2, 2026 at 06:00PM
SOURCE: PSYPOST.ORG

** Research quality varies widely from fantastic to small exploratory studies. Please check research methods when conclusions are very important to you. **
-------------------------------------------------

TITLE: Psilocybin therapy shows strong potential for treating cocaine addiction

URL: https://www.psypost.org/psilocybin-therapy-shows-strong-potential-for-treating-cocaine-addiction/

Two newly published studies suggest that psychedelic compounds may offer a novel approach to treating cocaine addiction. A clinical trial published in JAMA Network Open found that psilocybin combined with psychotherapy helped people stop using cocaine. A complementary animal study published in Addiction Biology indicates that while psychedelics can help unlearn drug-seeking behaviors, pairing them with the right environmental support might be needed to prevent long-term relapse.

Cocaine use disorder is a chronic condition in which a person compulsively seeks and uses cocaine despite negative consequences to their health, finances, and personal life. Medical treatments for the disorder have long been lacking. For example, a 2021 review evaluated available treatments for cocaine addiction, highlighting that few medical options successfully help people stop using the drug.

To address this gap, researchers have begun exploring classic psychedelics. Psilocybin is the main psychoactive compound found in certain types of mushrooms, known for altering perception, mood, and cognitive processes. Recent studies have tested its potential to treat various substance use disorders by combining the drug with professional psychological support.

The results from these trials have been encouraging. For instance, a 2022 clinical trial found that psilocybin combined with therapy substantially reduced heavy drinking in people with alcohol addiction. Similarly, a 2026 trial found that the treatment helped people quit smoking cigarettes at much higher rates than standard nicotine patches.

Building on this research progression, scientists wanted to test whether psilocybin could yield similar benefits for cocaine use disorder. At the same time, preclinical researchers, who conduct studies using animal or lab models before testing in humans, sought to understand exactly how psychedelics influence the biological and behavioral mechanisms of addiction in isolation, without the influence of human psychotherapy.

The human clinical trial was led by Peter S. Hendricks at the University of Alabama at Birmingham. The team recruited 40 adults diagnosed with cocaine use disorder who wanted to quit using the drug. The participants were randomly assigned to receive either a single oral dose of psilocybin or an active placebo. An active placebo is a control substance that produces mild noticeable side effects so participants cannot easily guess they received a fake treatment. In this case, the placebo was a dose of diphenhydramine, a common antihistamine.

Both groups participated in a structured psychotherapy program that included cognitive-behavioral techniques, which are therapy methods that help people identify and change harmful thought patterns and behaviors. They attended preparation sessions before the drug administration day and integration sessions afterward to process their experiences. The researchers specifically recruited individuals from demographic groups that are often underrepresented in psychedelic research. In the final sample, 82.5 percent of participants were Black, and 65 percent reported an annual income of $20,000 or less.

The findings suggest that psilocybin paired with therapy provides a strong protective effect against cocaine use. Over the 180 days following the treatment session, participants in the psilocybin group reported substantially more days without using cocaine compared to the placebo group. During the final three months of the study, the psilocybin group had about 28 more abstinent days out of every 100 days than the control group.

Additionally, the treatment helped a portion of participants stop using the drug entirely. Over the 180-day follow-up, 30 percent of those who received psilocybin maintained complete abstinence from cocaine. By comparison, none of the participants in the placebo group achieved complete abstinence over that same period.

To understand the isolated pharmacological effects of these treatments, meaning how the drugs interact chemically with the body and brain, a related animal study was led by Isis Rita Anzel Koutrouli at the National Institute of Mental Health in the Czech Republic. The team investigated how psilocybin and a different psychedelic compound, ibogaine, alter the learning processes associated with addiction. Ibogaine is a psychoactive substance derived from an African shrub that has been historically noted for its potential anti-addictive properties, though it operates differently in the brain than psilocybin.

The researchers trained male Wistar rats, a specific and widely used laboratory strain of white albino rats, to self-administer cocaine by pressing a lever. After the rats developed a reliable cocaine habit, the researchers initiated an extinction phase. During this phase, pressing the lever no longer provided the drug. The goal of extinction training is for the subject to unlearn the association between the action and the reward.

On the first and fifth days of the extinction phase, the rats were given injections of either psilocybin, ibogaine, or a saline placebo. Both psychedelics accelerated the extinction process. Rats treated with ibogaine pressed the lever less frequently starting after the first dose. Those treated with psilocybin showed a similar reduction in drug-seeking behavior following the second dose. Both drugs seemed to stabilize the animals’ behavior, helping them abandon the futile lever-pressing habit more efficiently than the placebo group.

The effects, however, did not translate to total relapse prevention. Six days after the final psychedelic dose, the researchers tested the rats by reintroducing the lights and sounds that had previously been paired with cocaine delivery. This triggers cue-induced reinstatement, a model of relapse. When faced with these triggers, the rats treated with psychedelics resumed pressing the lever just as frequently as the rats given the placebo.

These animal results highlight a nuanced reality about psychedelic treatments. The pharmacological effects of compounds like psilocybin and ibogaine appear to enhance behavioral flexibility, making it easier to break old habits. Yet, without the continuous environmental support or active psychotherapy provided in the human trial, the drugs alone did not block the urge to relapse when familiar drug cues returned.

The success seen in the human trial is in line with research covered by PsyPost in 2025, which found that a single dose of psilocybin paired with psychotherapy substantially reduced heavy drinking days in individuals with alcohol use disorder. The results also align with a 2026 study covered by PsyPost, which found that psilocybin and counseling produced higher rates of verified abstinence in cigarette smokers compared to standard nicotine patches.

As with all research, there are a few things to keep in mind. The human clinical trial featured a relatively small number of participants, which means the exact size of the treatment effect could vary in larger populations. Additionally, it is difficult to keep participants unaware of which treatment they receive in psychedelic studies, as the perceptual effects of the drug are very obvious. In this trial, 90 percent of the participants in the psilocybin group correctly guessed their assignment, which introduces the possibility that their expectations influenced their outcomes.

For the animal study, the researchers only tested male rats to avoid behavioral variations related to reproductive cycles. Testing female animals in the future will be necessary to see if the extinction-enhancing effects apply universally. The animal model also strips away the psychological and social elements of human addiction treatment. The rats did not receive the equivalent of human psychotherapy, which might be exactly why the drugs failed to protect them from cue-induced relapse.

Future research will need to test these interventions in larger, more diverse human samples to confirm the benefits. Scientists also hope to refine animal models to better understand how therapeutic environments interact with the biological changes caused by psychedelics.

The study, “Psilocybin in the Treatment of Cocaine Use Disorder: A Randomized Clinical Trial,” was authored by Peter S. Hendricks, Sara N. Lappan, Richard C. Shelton, Adrienne C. Lahti, Karen L. Cropsey, Matthew W. Johnson, Melissa Bradley, Otto Simonsson, Lori L. Davis, Daniel H. Grossman, and Cynthia E. Ortiz.

The study, “Psilocybin and Ibogaine in Cocaine-Seeking: Extinction Enhancement Without Relapse Prevention,” was authored by Isis Rita Anzel Koutrouli, Vojtěch Brejtr, Marek Schwendt, Kacper Witek, Chrysostomos Charalambous, Kristýna Aleksič, Nina Miniariková, Eva Lhotková, Martin Toman, Marek Nikolič, Radek Jurok, Petra Cihlářová, Vladimír Mazoch, Pavel Ryšánek, Martin Kuchař, Klára Šíchová, and Tomáš Páleníček.

URL: https://www.psypost.org/psilocybin-therapy-shows-strong-potential-for-treating-cocaine-addiction/

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#psychology #counseling #socialwork #psychotherapy @psychotherapist @psychotherapists @psychology @socialpsych @socialwork @psychiatry #mentalhealth #psychiatry #healthcare #depression #psychotherapist #PsilocybinTherapy #CocaineUseDisorder #PsychedelicResearch # AddictionTreatment #PsychotherapySupport #AbruptRelapsePrevention #AlcoholNicotineCocaine #ExtinctionTraining #PsyPost #ClinicalTrialResults

DATE: September 2, 2026 at 06:00PM
SOURCE: PSYPOST.ORG

** Research quality varies widely from fantastic to small exploratory studies. Please check research methods when conclusions are very important to you. **
-------------------------------------------------

TITLE: Psilocybin therapy shows strong potential for treating cocaine addiction

URL: https://www.psypost.org/psilocybin-therapy-shows-strong-potential-for-treating-cocaine-addiction/

Two newly published studies suggest that psychedelic compounds may offer a novel approach to treating cocaine addiction. A clinical trial published in JAMA Network Open found that psilocybin combined with psychotherapy helped people stop using cocaine. A complementary animal study published in Addiction Biology indicates that while psychedelics can help unlearn drug-seeking behaviors, pairing them with the right environmental support might be needed to prevent long-term relapse.

Cocaine use disorder is a chronic condition in which a person compulsively seeks and uses cocaine despite negative consequences to their health, finances, and personal life. Medical treatments for the disorder have long been lacking. For example, a 2021 review evaluated available treatments for cocaine addiction, highlighting that few medical options successfully help people stop using the drug.

To address this gap, researchers have begun exploring classic psychedelics. Psilocybin is the main psychoactive compound found in certain types of mushrooms, known for altering perception, mood, and cognitive processes. Recent studies have tested its potential to treat various substance use disorders by combining the drug with professional psychological support.

The results from these trials have been encouraging. For instance, a 2022 clinical trial found that psilocybin combined with therapy substantially reduced heavy drinking in people with alcohol addiction. Similarly, a 2026 trial found that the treatment helped people quit smoking cigarettes at much higher rates than standard nicotine patches.

Building on this research progression, scientists wanted to test whether psilocybin could yield similar benefits for cocaine use disorder. At the same time, preclinical researchers, who conduct studies using animal or lab models before testing in humans, sought to understand exactly how psychedelics influence the biological and behavioral mechanisms of addiction in isolation, without the influence of human psychotherapy.

The human clinical trial was led by Peter S. Hendricks at the University of Alabama at Birmingham. The team recruited 40 adults diagnosed with cocaine use disorder who wanted to quit using the drug. The participants were randomly assigned to receive either a single oral dose of psilocybin or an active placebo. An active placebo is a control substance that produces mild noticeable side effects so participants cannot easily guess they received a fake treatment. In this case, the placebo was a dose of diphenhydramine, a common antihistamine.

Both groups participated in a structured psychotherapy program that included cognitive-behavioral techniques, which are therapy methods that help people identify and change harmful thought patterns and behaviors. They attended preparation sessions before the drug administration day and integration sessions afterward to process their experiences. The researchers specifically recruited individuals from demographic groups that are often underrepresented in psychedelic research. In the final sample, 82.5 percent of participants were Black, and 65 percent reported an annual income of $20,000 or less.

The findings suggest that psilocybin paired with therapy provides a strong protective effect against cocaine use. Over the 180 days following the treatment session, participants in the psilocybin group reported substantially more days without using cocaine compared to the placebo group. During the final three months of the study, the psilocybin group had about 28 more abstinent days out of every 100 days than the control group.

Additionally, the treatment helped a portion of participants stop using the drug entirely. Over the 180-day follow-up, 30 percent of those who received psilocybin maintained complete abstinence from cocaine. By comparison, none of the participants in the placebo group achieved complete abstinence over that same period.

To understand the isolated pharmacological effects of these treatments, meaning how the drugs interact chemically with the body and brain, a related animal study was led by Isis Rita Anzel Koutrouli at the National Institute of Mental Health in the Czech Republic. The team investigated how psilocybin and a different psychedelic compound, ibogaine, alter the learning processes associated with addiction. Ibogaine is a psychoactive substance derived from an African shrub that has been historically noted for its potential anti-addictive properties, though it operates differently in the brain than psilocybin.

The researchers trained male Wistar rats, a specific and widely used laboratory strain of white albino rats, to self-administer cocaine by pressing a lever. After the rats developed a reliable cocaine habit, the researchers initiated an extinction phase. During this phase, pressing the lever no longer provided the drug. The goal of extinction training is for the subject to unlearn the association between the action and the reward.

On the first and fifth days of the extinction phase, the rats were given injections of either psilocybin, ibogaine, or a saline placebo. Both psychedelics accelerated the extinction process. Rats treated with ibogaine pressed the lever less frequently starting after the first dose. Those treated with psilocybin showed a similar reduction in drug-seeking behavior following the second dose. Both drugs seemed to stabilize the animals’ behavior, helping them abandon the futile lever-pressing habit more efficiently than the placebo group.

The effects, however, did not translate to total relapse prevention. Six days after the final psychedelic dose, the researchers tested the rats by reintroducing the lights and sounds that had previously been paired with cocaine delivery. This triggers cue-induced reinstatement, a model of relapse. When faced with these triggers, the rats treated with psychedelics resumed pressing the lever just as frequently as the rats given the placebo.

These animal results highlight a nuanced reality about psychedelic treatments. The pharmacological effects of compounds like psilocybin and ibogaine appear to enhance behavioral flexibility, making it easier to break old habits. Yet, without the continuous environmental support or active psychotherapy provided in the human trial, the drugs alone did not block the urge to relapse when familiar drug cues returned.

The success seen in the human trial is in line with research covered by PsyPost in 2025, which found that a single dose of psilocybin paired with psychotherapy substantially reduced heavy drinking days in individuals with alcohol use disorder. The results also align with a 2026 study covered by PsyPost, which found that psilocybin and counseling produced higher rates of verified abstinence in cigarette smokers compared to standard nicotine patches.

As with all research, there are a few things to keep in mind. The human clinical trial featured a relatively small number of participants, which means the exact size of the treatment effect could vary in larger populations. Additionally, it is difficult to keep participants unaware of which treatment they receive in psychedelic studies, as the perceptual effects of the drug are very obvious. In this trial, 90 percent of the participants in the psilocybin group correctly guessed their assignment, which introduces the possibility that their expectations influenced their outcomes.

For the animal study, the researchers only tested male rats to avoid behavioral variations related to reproductive cycles. Testing female animals in the future will be necessary to see if the extinction-enhancing effects apply universally. The animal model also strips away the psychological and social elements of human addiction treatment. The rats did not receive the equivalent of human psychotherapy, which might be exactly why the drugs failed to protect them from cue-induced relapse.

Future research will need to test these interventions in larger, more diverse human samples to confirm the benefits. Scientists also hope to refine animal models to better understand how therapeutic environments interact with the biological changes caused by psychedelics.

The study, “Psilocybin in the Treatment of Cocaine Use Disorder: A Randomized Clinical Trial,” was authored by Peter S. Hendricks, Sara N. Lappan, Richard C. Shelton, Adrienne C. Lahti, Karen L. Cropsey, Matthew W. Johnson, Melissa Bradley, Otto Simonsson, Lori L. Davis, Daniel H. Grossman, and Cynthia E. Ortiz.

The study, “Psilocybin and Ibogaine in Cocaine-Seeking: Extinction Enhancement Without Relapse Prevention,” was authored by Isis Rita Anzel Koutrouli, Vojtěch Brejtr, Marek Schwendt, Kacper Witek, Chrysostomos Charalambous, Kristýna Aleksič, Nina Miniariková, Eva Lhotková, Martin Toman, Marek Nikolič, Radek Jurok, Petra Cihlářová, Vladimír Mazoch, Pavel Ryšánek, Martin Kuchař, Klára Šíchová, and Tomáš Páleníček.

URL: https://www.psypost.org/psilocybin-therapy-shows-strong-potential-for-treating-cocaine-addiction/

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#psychology #counseling #socialwork #psychotherapy @psychotherapist @psychotherapists @psychology @socialpsych @socialwork @psychiatry #mentalhealth #psychiatry #healthcare #depression #psychotherapist #PsilocybinTherapy #CocaineUseDisorder #PsychedelicResearch # AddictionTreatment #PsychotherapySupport #AbruptRelapsePrevention #AlcoholNicotineCocaine #ExtinctionTraining #PsyPost #ClinicalTrialResults

DATE: September 2, 2026 at 06:00PM
SOURCE: PSYPOST.ORG

** Research quality varies widely from fantastic to small exploratory studies. Please check research methods when conclusions are very important to you. **
-------------------------------------------------

TITLE: Psilocybin therapy shows strong potential for treating cocaine addiction

URL: https://www.psypost.org/psilocybin-therapy-shows-strong-potential-for-treating-cocaine-addiction/

Two newly published studies suggest that psychedelic compounds may offer a novel approach to treating cocaine addiction. A clinical trial published in JAMA Network Open found that psilocybin combined with psychotherapy helped people stop using cocaine. A complementary animal study published in Addiction Biology indicates that while psychedelics can help unlearn drug-seeking behaviors, pairing them with the right environmental support might be needed to prevent long-term relapse.

Cocaine use disorder is a chronic condition in which a person compulsively seeks and uses cocaine despite negative consequences to their health, finances, and personal life. Medical treatments for the disorder have long been lacking. For example, a 2021 review evaluated available treatments for cocaine addiction, highlighting that few medical options successfully help people stop using the drug.

To address this gap, researchers have begun exploring classic psychedelics. Psilocybin is the main psychoactive compound found in certain types of mushrooms, known for altering perception, mood, and cognitive processes. Recent studies have tested its potential to treat various substance use disorders by combining the drug with professional psychological support.

The results from these trials have been encouraging. For instance, a 2022 clinical trial found that psilocybin combined with therapy substantially reduced heavy drinking in people with alcohol addiction. Similarly, a 2026 trial found that the treatment helped people quit smoking cigarettes at much higher rates than standard nicotine patches.

Building on this research progression, scientists wanted to test whether psilocybin could yield similar benefits for cocaine use disorder. At the same time, preclinical researchers, who conduct studies using animal or lab models before testing in humans, sought to understand exactly how psychedelics influence the biological and behavioral mechanisms of addiction in isolation, without the influence of human psychotherapy.

The human clinical trial was led by Peter S. Hendricks at the University of Alabama at Birmingham. The team recruited 40 adults diagnosed with cocaine use disorder who wanted to quit using the drug. The participants were randomly assigned to receive either a single oral dose of psilocybin or an active placebo. An active placebo is a control substance that produces mild noticeable side effects so participants cannot easily guess they received a fake treatment. In this case, the placebo was a dose of diphenhydramine, a common antihistamine.

Both groups participated in a structured psychotherapy program that included cognitive-behavioral techniques, which are therapy methods that help people identify and change harmful thought patterns and behaviors. They attended preparation sessions before the drug administration day and integration sessions afterward to process their experiences. The researchers specifically recruited individuals from demographic groups that are often underrepresented in psychedelic research. In the final sample, 82.5 percent of participants were Black, and 65 percent reported an annual income of $20,000 or less.

The findings suggest that psilocybin paired with therapy provides a strong protective effect against cocaine use. Over the 180 days following the treatment session, participants in the psilocybin group reported substantially more days without using cocaine compared to the placebo group. During the final three months of the study, the psilocybin group had about 28 more abstinent days out of every 100 days than the control group.

Additionally, the treatment helped a portion of participants stop using the drug entirely. Over the 180-day follow-up, 30 percent of those who received psilocybin maintained complete abstinence from cocaine. By comparison, none of the participants in the placebo group achieved complete abstinence over that same period.

To understand the isolated pharmacological effects of these treatments, meaning how the drugs interact chemically with the body and brain, a related animal study was led by Isis Rita Anzel Koutrouli at the National Institute of Mental Health in the Czech Republic. The team investigated how psilocybin and a different psychedelic compound, ibogaine, alter the learning processes associated with addiction. Ibogaine is a psychoactive substance derived from an African shrub that has been historically noted for its potential anti-addictive properties, though it operates differently in the brain than psilocybin.

The researchers trained male Wistar rats, a specific and widely used laboratory strain of white albino rats, to self-administer cocaine by pressing a lever. After the rats developed a reliable cocaine habit, the researchers initiated an extinction phase. During this phase, pressing the lever no longer provided the drug. The goal of extinction training is for the subject to unlearn the association between the action and the reward.

On the first and fifth days of the extinction phase, the rats were given injections of either psilocybin, ibogaine, or a saline placebo. Both psychedelics accelerated the extinction process. Rats treated with ibogaine pressed the lever less frequently starting after the first dose. Those treated with psilocybin showed a similar reduction in drug-seeking behavior following the second dose. Both drugs seemed to stabilize the animals’ behavior, helping them abandon the futile lever-pressing habit more efficiently than the placebo group.

The effects, however, did not translate to total relapse prevention. Six days after the final psychedelic dose, the researchers tested the rats by reintroducing the lights and sounds that had previously been paired with cocaine delivery. This triggers cue-induced reinstatement, a model of relapse. When faced with these triggers, the rats treated with psychedelics resumed pressing the lever just as frequently as the rats given the placebo.

These animal results highlight a nuanced reality about psychedelic treatments. The pharmacological effects of compounds like psilocybin and ibogaine appear to enhance behavioral flexibility, making it easier to break old habits. Yet, without the continuous environmental support or active psychotherapy provided in the human trial, the drugs alone did not block the urge to relapse when familiar drug cues returned.

The success seen in the human trial is in line with research covered by PsyPost in 2025, which found that a single dose of psilocybin paired with psychotherapy substantially reduced heavy drinking days in individuals with alcohol use disorder. The results also align with a 2026 study covered by PsyPost, which found that psilocybin and counseling produced higher rates of verified abstinence in cigarette smokers compared to standard nicotine patches.

As with all research, there are a few things to keep in mind. The human clinical trial featured a relatively small number of participants, which means the exact size of the treatment effect could vary in larger populations. Additionally, it is difficult to keep participants unaware of which treatment they receive in psychedelic studies, as the perceptual effects of the drug are very obvious. In this trial, 90 percent of the participants in the psilocybin group correctly guessed their assignment, which introduces the possibility that their expectations influenced their outcomes.

For the animal study, the researchers only tested male rats to avoid behavioral variations related to reproductive cycles. Testing female animals in the future will be necessary to see if the extinction-enhancing effects apply universally. The animal model also strips away the psychological and social elements of human addiction treatment. The rats did not receive the equivalent of human psychotherapy, which might be exactly why the drugs failed to protect them from cue-induced relapse.

Future research will need to test these interventions in larger, more diverse human samples to confirm the benefits. Scientists also hope to refine animal models to better understand how therapeutic environments interact with the biological changes caused by psychedelics.

The study, “Psilocybin in the Treatment of Cocaine Use Disorder: A Randomized Clinical Trial,” was authored by Peter S. Hendricks, Sara N. Lappan, Richard C. Shelton, Adrienne C. Lahti, Karen L. Cropsey, Matthew W. Johnson, Melissa Bradley, Otto Simonsson, Lori L. Davis, Daniel H. Grossman, and Cynthia E. Ortiz.

The study, “Psilocybin and Ibogaine in Cocaine-Seeking: Extinction Enhancement Without Relapse Prevention,” was authored by Isis Rita Anzel Koutrouli, Vojtěch Brejtr, Marek Schwendt, Kacper Witek, Chrysostomos Charalambous, Kristýna Aleksič, Nina Miniariková, Eva Lhotková, Martin Toman, Marek Nikolič, Radek Jurok, Petra Cihlářová, Vladimír Mazoch, Pavel Ryšánek, Martin Kuchař, Klára Šíchová, and Tomáš Páleníček.

URL: https://www.psypost.org/psilocybin-therapy-shows-strong-potential-for-treating-cocaine-addiction/

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#psychology #counseling #socialwork #psychotherapy @psychotherapist @psychotherapists @psychology @socialpsych @socialwork @psychiatry #mentalhealth #psychiatry #healthcare #depression #psychotherapist #PsilocybinTherapy #CocaineUseDisorder #PsychedelicResearch # AddictionTreatment #PsychotherapySupport #AbruptRelapsePrevention #AlcoholNicotineCocaine #ExtinctionTraining #PsyPost #ClinicalTrialResults

DATE: August 22, 2026 at 04:00PM
SOURCE: PSYPOST.ORG

** Research quality varies widely from fantastic to small exploratory studies. Please check research methods when conclusions are very important to you. **
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TITLE: Psychedelic raves act as a modern rite of passage with complex psychological effects, new research suggests

URL: https://www.psypost.org/psychedelic-raves-act-as-a-modern-rite-of-passage-with-complex-psychological-effects-new-research-suggests/

For frequent Israeli rave-goers who consume psychedelic drugs, the experience extends well beyond the hours spent dancing, with preparations beginning beforehand and physical, emotional, and social effects continuing after the party, according to a qualitative study in the Journal of Substance Use and Addiction Treatment. Participants described both positive experiences, including greater confidence and social connection, and negative effects such as exhaustion, nausea, low mood, and problems concentrating.

Rave parties combine electronic dance music, prolonged dancing, and often highly stimulating social and visual environments. Psychedelic and other psychoactive drug use is also common in some rave settings. Previous research has documented risks such as adverse drug reactions alongside reports of belonging, identity change, and meaningful or transformative experiences.

Yet researchers have typically focused on what people experience while they are actually at a rave. Far less is known about the period before attendees arrive or what happens as they return to ordinary routines afterward. That gap is particularly important because preparation can influence drug-related risk, while difficult physical or psychological after-effects may not become apparent until the event is over.

Led by Yula Milshteyn of Bar-Ilan University in Israel, the researchers interviewed 27 Jewish Israeli rave attendees who regularly attended events and consumed psychedelic drugs. Participants were, on average, 38.3 years old; 18 were men and nine were women. Ten reported using MDMA at raves, 15 reported LSD, and two described using LSD or MDMA together with substances such as alcohol or marijuana.

Rather than using questionnaires with predetermined answers, the researchers conducted semi-structured interviews and analyzed how participants described and interpreted their own experiences. The approach produced five broad themes before a rave and four afterward.

Milshteyn and Bensimon discovered that preparation was not merely practical. Participants described physical rituals and drug-related preparation, excitement and mixed bodily feelings, attempts to clear negative thoughts, social bonding with friends, and practical activities such as organizing food, clothing, water, and tents. The researchers interpreted these practices through the idea of a “rite of passage”: temporarily leaving ordinary routines before entering a distinctive social setting.

Afterward, experiences were equally varied. Participants reported tiredness, dizziness, headaches, nausea, and vomiting in the days following events. Emotional accounts included joy, confidence, and empowerment, as well as less welcome experiences such as depression-like low mood and mood swings. Some people described positive changes in their creative or musical direction, while others reported reduced concentration and attention. Enhanced friendships and sociability formed another recurring theme.

The study therefore does not support a simple portrayal of rave experiences as either beneficial or harmful. The same participants could describe meaningful social or emotional changes alongside unpleasant physical and psychological consequences.

The researchers concluded that after the raves, “participants return to their normal life, yet with changes in physical, emotional, cognitive, and social aspects.”

Some limitations must be accounted for. For example, the sample was small, self-selected, and predominantly male. Furthermore, exact drug doses were not recorded, and no objective measurements of participants’ psychological or cognitive states were collected.

The study, “Preparations for rave music parties and consequences for attendees who consume psychedelic drugs,” was authored by Yula Milshteyn and Moshe Bensimon.

URL: https://www.psypost.org/psychedelic-raves-act-as-a-modern-rite-of-passage-with-complex-psychological-effects-new-research-suggests/

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