Psilocybin for Opioid Use Disorder
(BIPOD-Out Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Johns Hopkins University
Must be taking: Buprenorphine
Must not be taking: Antidepressants, Methadone, Naltrexone, others
Disqualifiers: Hypertension, Epilepsy, Diabetes, Schizophrenia, others
Stay on Your Current Meds
No Placebo Group
Prior Safety Data
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?This study will examine the effect of a single high dose of psilocybin therapy (30 mg) versus a very low dose (1 mg) as an adjunctive therapy to individuals undergoing standard-of-care outpatient buprenorphine treatment for Opioid use disorder (OUD). The participants will have previously undergone buprenorphine induction before. Effects of adjunctive psilocybin will be determined for longitudinal outcomes of opioid abstinence, compliance with outpatient buprenorphine maintenance, quality of life, and mood.
Do I need to stop taking my current medications for the trial?
Yes, you may need to stop taking certain medications. The trial requires that you are not on antidepressants, certain medications affecting serotonin, methadone, naltrexone, or specific enzyme inhibitors. If you take these intermittently, you must wait for a period without them before participating.
What data supports the effectiveness of the drug psilocybin for treating opioid use disorder?
Research shows that psilocybin has been studied for various psychiatric disorders, including substance use disorders, and has shown promising results with marked, long-term improvements in some patients. However, more research is needed to determine its effectiveness specifically for opioid use disorder.
12345Is psilocybin safe for human use?
Psilocybin has been studied for its safety in humans, showing that while it can cause challenging experiences or 'bad trips,' the risk of lasting psychological distress is low when used in controlled settings with proper support. In clinical trials, psilocybin has been generally well-tolerated, but it can cause temporary hallucinations and changes in perception.
16789How does the drug psilocybin differ from other treatments for opioid use disorder?
Psilocybin is unique because it is a psychedelic compound found in 'magic mushrooms' that works by affecting serotonin receptors in the brain, which is different from traditional opioid treatments that often focus on blocking opioid receptors or reducing withdrawal symptoms. It has shown promise in treating various mental health conditions, suggesting a novel approach to addressing the psychological aspects of addiction.
127810Eligibility Criteria
This trial is for adults aged 21-70 with Opioid Use Disorder who are fluent in English, willing to undergo or have recently completed buprenorphine induction, and not at high risk for suicide. Participants must meet DSM-5 criteria for OUD, be off antidepressants for a certain period, have prior buprenorphine maintenance experience, test positive for opioids in urine tests, and have stable housing.Inclusion Criteria
I haven't taken antidepressants for their full withdrawal period before joining.
Can read, write, and speak English fluently
I am willing to start or have started buprenorphine treatment in the last 3 weeks.
+9 more
Exclusion Criteria
Current or past history of meeting DSM-5 criteria for Schizophrenia, Psychotic Disorder (unless substance-induced or due to a medical condition), Bipolar I or II Disorder or Major Depression with psychotic features
I have heart or blood vessel problems, like high blood pressure, chest pain, or a recent stroke.
I have been on buprenorphine for more than 3 weeks.
+17 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-3 weeks
Buprenorphine Induction
Participants undergo standard-of-care outpatient buprenorphine induction
3 weeks
Psilocybin Administration
Participants receive either a high dose (30 mg) or a very low dose (1 mg) of psilocybin under double-blind conditions
1 day
1 visit (in-person)
Outpatient Buprenorphine Maintenance
Participants undergo an 8-week outpatient phase with standard-of-care buprenorphine maintenance
8 weeks
6 visits (in-person) at 1, 2, 3, 4, 6, and 8 weeks post-dosing
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 to 6 months
Participant Groups
The study is testing the effects of a single high dose (30 mg) versus a very low dose (1 mg) of psilocybin therapy as an add-on to standard outpatient buprenorphine treatment. It aims to see how psilocybin affects opioid abstinence rates, adherence to buprenorphine maintenance programs, quality of life improvements, and mood changes over time.
2Treatment groups
Experimental Treatment
Active Control
Group I: High-dose psilocybin + buprenorphineExperimental Treatment1 Intervention
High-dose psilocybin (30 mg) session following standard-of-care outpatient buprenorphine induction
Group II: Very low-dose psilocybin + buprenorphineActive Control1 Intervention
Very low dose psilocybin session (1 mg) following standard-of-care outpatient buprenorphine induction
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Johns Hopkins Center for Psychedelic and Consciousness ResearchBaltimore, MD
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Who Is Running the Clinical Trial?
Johns Hopkins UniversityLead Sponsor
References
The pharmacology of psilocybin. [2016]Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) is the major psychoactive alkaloid of some species of mushrooms distributed worldwide. These mushrooms represent a growing problem regarding hallucinogenic drug abuse. Despite its experimental medical use in the 1960s, only very few pharmacological data about psilocybin were known until recently. Because of its still growing capacity for abuse and the widely dispersed data this review presents all the available pharmacological data about psilocybin.
Psilocybin in Palliative Care: An Update. [2023]This review article summarizes clinically and socially relevant developments over the past five years in the therapeutic use of the classical tryptamine psychedelic substance psilocybin, with respect to the common challenges faced by palliative care patients and their care teams. Psilocybin is available in whole fungal and isolated forms but is not yet approved for therapeutic use in the United States. Using targeted database and gray literature searches, and author recall, key sources were identified, reviewed, and synthesized as to the safety and efficacy of psilocybin in palliative care.
Metabolism of psilocybin and psilocin: clinical and forensic toxicological relevance. [2018]Psilocybin and psilocin are controlled substances in many countries. These are the two main hallucinogenic compounds of the "magic mushrooms" and both act as agonists or partial agonists at 5-hydroxytryptamine (5-HT)2A subtype receptors. During the last few years, psilocybin and psilocin have gained therapeutic relevance but considerable physiological variability between individuals that can influence dose-response and toxicological profile has been reported. This review aims to discuss metabolism of psilocybin and psilocin, by presenting all major and minor psychoactive metabolites. Psilocybin is primarily a pro-drug that is dephosphorylated by alkaline phosphatase to active metabolite psilocin. This last is then further metabolized, psilocin-O-glucuronide being the main urinary metabolite with clinical and forensic relevance in diagnosis.
[Treatment with psilocybin: applications for patients with psychiatric disorders]. [2021]After a cessation of almost 40 years, there is renewed interest into therapeutic applicationsof the serotonergic psychedelic psilocybin for the treatment of patients with various psychiatric disorders. PubMed was searched for clinical trials into "psilocybin" between 2000 and 2020, complemented by handsearching. Articles were also screened for explanatory models and working mechanisms. Psilocybin has been studied in 9 clinical trials: for the treatment of substance use disorders, depression, end-of-life anxiety, demoralization, and obsessive-compulsive disorder. Results show that psilocybin is well tolerated, with only limited side-effects, while even patients with treatment-resistant disorders sometimes show marked, long-term improvements after one or a few sessions. Initial results are encouraging, but there are several limitations. More research is needed to determine which patient populations can benefit, what role setting and the placebo response play, and how these novel treatments can be optimized.
Dose-response relationships of psilocybin-induced subjective experiences in humans. [2022]Label="BACKGROUND" NlmCategory="BACKGROUND">Psilocybin is the psychoactive component in Psilocybe mushrooms ('magic mushrooms'). Whether and how the quality of the psilocybin-induced experience might mediate beneficial health outcomes is currently under investigation, for example, in therapeutic applications. However, to date, no meta-analysis has investigated the dose-dependency of subjective experiences across available studies.
Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences. [2018]Acute and enduring adverse effects of psilocybin have been reported anecdotally, but have not been well characterized. For this study, 1993 individuals (mean age 30 yrs; 78% male) completed an online survey about their single most psychologically difficult or challenging experience (worst "bad trip") after consuming psilocybin mushrooms. Thirty-nine percent rated it among the top five most challenging experiences of his/her lifetime. Eleven percent put self or others at risk of physical harm; factors increasing the likelihood of risk included estimated dose, duration and difficulty of the experience, and absence of physical comfort and social support. Of the respondents, 2.6% behaved in a physically aggressive or violent manner and 2.7% received medical help. Of those whose experience occurred >1 year before, 7.6% sought treatment for enduring psychological symptoms. Three cases appeared associated with onset of enduring psychotic symptoms and three cases with attempted suicide. Multiple regression analysis showed degree of difficulty was positively associated, and duration was negatively associated, with enduring increases in well-being. Difficulty of experience was positively associated with dose. Despite difficulties, 84% endorsed benefiting from the experience. The incidence of risky behavior or enduring psychological distress is extremely low when psilocybin is given in laboratory studies to screened, prepared, and supported participants.
Pharmacokinetics of Escalating Doses of Oral Psilocybin in Healthy Adults. [2022]Psilocybin is a psychedelic tryptamine that has shown promise in recent clinical trials for the treatment of depression and substance use disorders. This open-label study of the pharmacokinetics of psilocybin was performed to describe the pharmacokinetics and safety profile of psilocybin in sequential, escalating oral doses of 0.3, 0.45, and 0.6 mg/kg in 12 healthy adults.
DARK Classics in Chemical Neuroscience: Psilocybin. [2019]Psilocybin is found in a family of mushrooms commonly known as "magic mushrooms" that have been used throughout history to induce hallucinations. In the late 1950s Albert Hofmann, of Sandoz Laboratories, identified and synthesized the psychoactive compounds psilocybin and psilocin which are found in psilocybe mushrooms. Psilocybin was marketed by Sandoz as Indocybin for basic psychopharmacological and therapeutic clinical research. Psilocybin saw a rapid rise in popularity during the 1960s and was classed as a Schedule I drug in 1970. This led to a significant decrease in psilocybin research. Recently, however, preliminary studies with psilocybin have shown promise as potential for the treatment of obsessive compulsive disorder, alcohol addiction, tobacco addiction, and major depressive disorder, and the treatment of depression in terminally ill cancer patients. This review describes in detail the synthesis, metabolism, pharmacology, adverse drug reactions, and importance of psilocybin to neuroscience in the past and present.
[Hallucinogenic mushrooms]. [2018]The group of hallucinogenic mushrooms (species of the genera Conocybe, Gymnopilus, Panaeolus, Pluteus, Psilocybe, and Stropharia) is psilocybin-containing mushrooms. These "magic", psychoactive fungi have the serotonergic hallucinogen psilocybin. Toxicity of these mushrooms is substantial because of the popularity of hallucinogens. Psilocybin and its active metabolite psilocin are similar to lysergic acid diethylamide. These hallucinogens affect the central nervous system rapidly (within 0.5-1 hour after ingestion), producing ataxia, hyperkinesis, and hallucinations. In this review article there are discussed about history of use of hallucinogenic mushrooms and epidemiology; pharmacology, pharmacodynamics, somatic effects and pharmacokinetics of psilocybin, the clinical effects of psilocybin and psilocin, signs and symptoms of ingestion of hallucinogenic mushrooms, treatment and prognosis.
Structure-Activity Relationships for Psilocybin, Baeocystin, Aeruginascin, and Related Analogues to Produce Pharmacological Effects in Mice. [2023]4-Phosphoryloxy-N,N-dimethyltryptamine (psilocybin) is a naturally occurring tertiary amine found in many mushroom species. Psilocybin is a prodrug for 4-hydroxy-N,N-dimethyltryptamine (psilocin), which induces psychedelic effects via agonist activity at the serotonin (5-HT) 2A receptor (5-HT2A). Several other 4-position ring-substituted tryptamines are present in psilocybin-containing mushrooms, including the secondary amine 4-phosphoryloxy-N-methyltryptamine (baeocystin) and the quaternary ammonium 4-phosphoryloxy-N,N,N-trimethyltryptamine (aeruginascin), but these compounds are not well studied. Here, we investigated the structure-activity relationships for psilocybin, baeocystin, and aeruginascin, as compared to their 4-acetoxy and 4-hydroxy analogues, using in vitro and in vivo methods. Broad receptor screening using radioligand binding assays in transfected cells revealed that secondary and tertiary tryptamines with either 4-acetoxy or 4-hydroxy substitutions display nanomolar affinity for most human 5-HT receptor subtypes tested, including the 5-HT2A and the serotonin 1A receptor (5-HT1A). The same compounds displayed affinity for 5-HT2A and 5-HT1A in mouse brain tissue in vitro and exhibited agonist efficacy in assays examining 5-HT2A-mediated calcium mobilization and β-arrestin 2 recruitment. In mouse experiments, only the tertiary amines psilocin, psilocybin, and 4-acetoxy-N,N-dimethyltryptamine (psilacetin) induced head twitch responses (ED50 0.11-0.29 mg/kg) indicative of psychedelic-like activity. Head twitches were blocked by 5-HT2A antagonist pretreatment, supporting 5-HT2A involvement. Both secondary and tertiary amines decreased body temperature and locomotor activity at higher doses, the effects of which were blocked by 5-HT1A antagonist pretreatment. Across all assays, the pharmacological effects of 4-acetoxy and 4-hydroxy compounds were similar, and these compounds were more potent than their 4-phosphoryloxy counterparts. Importantly, psilacetin appears to be a prodrug for psilocin that displays substantial serotonin receptor activities of its own.