Psilocybin for Quitting Smoking

Recruiting at 3 trial locations

Overseen By Peter Hendricks, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Johns Hopkins University

Must not be taking: Antidepressants, Antipsychotics, MAOIs, others

Disqualifiers: Pregnancy, Neurological illnesses, Schizophrenia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 2 weeks

66 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests psilocybin, a compound from mushrooms, to help smokers quit. It targets smokers because past studies showed good results. Psilocybin affects brain receptors to improve mood and reduce cravings, potentially making it easier to stop smoking. Psilocybin has shown promise in previous studies for promoting long-term smoking abstinence when combined with therapy.

Will I have to stop taking my current medications?

If you are currently taking antidepressants, antipsychotics, certain dietary supplements, or medications for smoking cessation, you will need to stop these before participating in the trial. For medications taken intermittently, you must wait until at least 5 half-lives of the medication have passed after the last dose before starting the trial.

Is psilocybin safe for humans?

Psilocybin has been studied for its safety in various conditions, including depression and substance use disorders, and is generally considered safe when used in controlled settings. However, it can cause hallucinations and other effects on the central nervous system, so it should be used under medical supervision to avoid potential risks. ^{1 2 3 4 5}

How is the drug psilocybin unique for quitting smoking?

Psilocybin, found in 'magic mushrooms', is unique for quitting smoking because it works by affecting serotonin receptors in the brain, which can lead to changes in perception and mood. Unlike traditional smoking cessation aids, psilocybin is a hallucinogen that may help by altering the user's mindset and potentially reducing cravings. ^{1 6 7 8 9}

What data supports the effectiveness of the drug psilocybin for quitting smoking?

Research shows that psilocybin, a compound found in certain mushrooms, has been trialed for various conditions like addiction, anxiety, and depression, suggesting potential benefits for quitting smoking. Additionally, psilocybin microdosing has been associated with mood and mental health improvements, which could support smoking cessation efforts. ^{1 6 10 11 12}

Who Is on the Research Team?

Matthew Johnson, Ph.D

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

This trial is for adults over 21 who smoke daily (at least 5 cigarettes/day) and have tried to quit multiple times without success. Participants must be in good health as confirmed by medical exams, not use other tobacco products or psychoactive drugs, including alcohol, before sessions. Pregnant or nursing women and those with certain mental health conditions or cardiovascular issues are excluded.

Inclusion Criteria

I am 21 years old or older.

I smoke at least 5 cigarettes daily, have tried to quit multiple times without success, and still want to quit.

Agree to refrain from using any psychoactive drugs, including alcoholic beverages, within 24 hours of psilocybin/niacin administration

Exclusion Criteria

I am currently taking antidepressants, antipsychotics, MAOIs, certain dietary supplements, or specific medications like phenytoin.

Use of e-cigarettes or tobacco products other than machine-manufactured combustible cigarettes on more than 5 of the previous 30 days

Positive urine drug screen for illicit drugs (excluding cannabis)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment

Participants receive either psilocybin or niacin in two sessions, 1 week apart, with cognitive behavior therapy (CBT) administered to both groups.

2 weeks

2 visits (in-person)

Follow-up

Participants are monitored for smoking cessation and cognitive control, with assessments at 12-month follow-up.

12 months

Multiple visits (in-person and virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Niacin
• Psilocybin

Trial Overview The study tests the effectiveness of psilocybin, a psychedelic compound, against niacin in helping people stop smoking. It's double-blind and randomized: participants won't know which treatment they receive during two sessions spaced one week apart at three research sites.

How Is the Trial Designed?

Group I: Psilocybin Active Control 1 Intervention

30 mg in session 1 and either 30 mg or 40 mg in session 2, with sessions 1 week apart. Dosing will be based on participants' responses to the Mystical Experiences Questionnaire (MEQ30), taken at the end of their first session. Participants with a score ≥60% of the maximum on the MEQ30 will remain at a dose of 30 mg of psilocybin for the second session. Participants with an MEQ30 score below 60% will receive a dose of 40 mg for the second session.

Group II: Niacin Active Control 1 Intervention

150 mg in session 1 and either 150 mg or 200 mg in session 2, with sessions 1 week apart. Dosing will be based on participants' responses to the Mystical Experiences Questionnaire (MEQ30), taken at the end of their first session. Participants with a score ≥60% of the maximum on the MEQ30 will remain at a dose of 150 mg niacin for the second session. Participants with an MEQ30 score below 60% will receive a dose of 200 mg niacin for the second session.

Niacin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Niacin for:

• Hyperlipidemia
• Pellagra

Approved in European Union as Niacin for:

• Hyperlipidemia
• Pellagra

Approved in Canada as Niacin for:

• Hyperlipidemia
• Pellagra

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Sheppard Pratt Health System

Collaborator

Trials

23

Recruited

7,800+

University of Alabama at Birmingham

Collaborator

Trials

1,677

Recruited

2,458,000+

New York University

Collaborator

Trials

249

Recruited

229,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

Psilocybin-containing mushrooms, commonly known as hallucinogenic or 'magic' mushrooms, rapidly affect the central nervous system within 0.5-1 hour of ingestion, leading to effects such as ataxia, hyperkinesis, and hallucinations.

The review discusses the significant toxicity associated with these mushrooms, highlighting the need for awareness and understanding of their pharmacology, clinical effects, and potential treatment for adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Hallucinogenic mushrooms]. Reingardiene, D., Vilcinskaite, J., Lazauskas, R.[2018]

Psilocybin, a compound found in certain mushrooms, is being studied for its potential therapeutic effects in treating conditions like addiction, anxiety, and depression, primarily through its active metabolite psilocin, which interacts with the 5HT2A receptor.

While psilocybin shows promise as a treatment agent in neuropsychiatry, careful consideration of its safety and potential for harm is necessary to determine its clinical use, highlighting the need for a responsible approach in this research area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin in neuropsychiatry: a review of its pharmacology, safety, and efficacy. Dodd, S., Norman, TR., Eyre, HA., et al.[2022]

A long-term follow-up of 15 participants from a previous trial showed that psilocybin-assisted psychotherapy led to sustained reductions in anxiety, depression, and other distressing symptoms, with 60-80% of participants still experiencing significant improvements 3.2 to 4.5 years later.

Participants reported that the psilocybin therapy was among the most meaningful experiences of their lives, indicating its potential to enhance psychological and spiritual well-being in patients facing life-threatening cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer. Agin-Liebes, GI., Malone, T., Yalch, MM., et al.[2023]

In a study of 953 psilocybin microdosers and 180 non-microdosing comparators over 30 days, participants reported small- to medium-sized improvements in mood and mental health, consistent across different demographics.

Combining psilocybin with lion's mane mushrooms and niacin showed specific psychomotor performance benefits in older adults, suggesting potential advantages of this combination, although further research is needed to confirm these effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin microdosers demonstrate greater observed improvements in mood and mental health at one month relative to non-microdosing controls. Rootman, JM., Kiraga, M., Kryskow, P., et al.[2022]

A meta-analysis of psilocybin studies found that higher doses of psilocybin are associated with stronger subjective experiences, particularly in areas like perceptual alterations and ego dissolution, based on data from standardized questionnaires.

Challenging experiences were less affected by dose, suggesting that individual and environmental factors also play a significant role in the psilocybin experience, indicating that these findings are most relevant in controlled settings rather than recreational use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-response relationships of psilocybin-induced subjective experiences in humans. Hirschfeld, T., Schmidt, TT.[2022]

There is a growing trend among young people to consume wild Psilocybin mushrooms for their hallucinogenic effects, but this practice carries risks.

The report highlights seven cases of mushroom overdosage, stressing that while Psilocybin mushrooms are generally considered harmless, there is a significant danger of accidentally consuming toxic mushroom species that can cause serious harm.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The danger of hallucinogenic mushrooms. Mills, PR., Lesinskas, D., Watkinson, G.[2017]

Psilocybin, a hallucinogenic compound found in certain mushrooms, has been associated with increasing rates of drug abuse, highlighting the need for comprehensive pharmacological understanding.

Despite its historical use in the 1960s for experimental medical purposes, recent research has only begun to uncover the pharmacological properties of psilocybin, indicating a gap in knowledge that needs to be addressed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacology of psilocybin. Passie, T., Seifert, J., Schneider, U., et al.[2016]

In a study involving 12 healthy adults, escalating doses of psilocybin (0.3, 0.45, and 0.6 mg/kg) were administered safely, with no serious adverse events reported, indicating a favorable safety profile for this psychedelic compound.

The pharmacokinetics of psilocin, the active metabolite of psilocybin, were linear across the tested doses, with an elimination half-life of about 3 hours, suggesting that no dose adjustments are necessary for individuals with mild to moderate renal impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of Escalating Doses of Oral Psilocybin in Healthy Adults. Brown, RT., Nicholas, CR., Cozzi, NV., et al.[2022]

A systematic review of 16 studies found that psilocybin is generally well-tolerated, with the most common side effects being transient nausea and headache, and no reports of severe long-term issues like psychosis.

Psilocybin shows promise as a safe treatment option for psychiatric and substance-dependence conditions, particularly for patients who do not respond to standard therapies, as it has demonstrated both acute and long-term safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Tolerability and Safety of Psilocybin in Psychiatric and Substance-Dependence Conditions: A Systematic Review. Kaminski, D., Reinert, JP.[2023]

Psilocybin, a naturally occurring compound similar to LSD, has been found to not cause serious health issues or dependency, suggesting a favorable safety profile.

Recent studies indicate that psilocybin may enhance feelings of wellbeing and is being investigated for its potential therapeutic effects on mood and anxiety disorders due to its action on the 5-HT2A serotonin receptors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of psilocybin in the treatment of depression. Mahapatra, A., Gupta, R.[2020]

Psilocybin, a compound found in 'magic mushrooms', has shown potential in recent studies for treating various mental health conditions, including obsessive-compulsive disorder, alcohol and tobacco addiction, and major depressive disorder, particularly in terminally ill cancer patients.

Despite its classification as a Schedule I drug in 1970, which halted much research, there is a renewed interest in psilocybin's therapeutic effects, highlighting its importance in both historical and contemporary neuroscience.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DARK Classics in Chemical Neuroscience: Psilocybin. Geiger, HA., Wurst, MG., Daniels, RN.[2019]

In a phase 2 trial with 104 participants, a single dose of psilocybin significantly reduced depression scores compared to a niacin placebo, showing a mean difference of -12.3 points on the MADRS scale by day 43, indicating strong efficacy.

Psilocybin treatment led to a significant reduction in functional disability as measured by the Sheehan Disability Scale, with no serious adverse events reported, suggesting it is a safe option when combined with psychological support for treating major depressive disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-Dose Psilocybin Treatment for Major Depressive Disorder: A Randomized Clinical Trial. Raison, CL., Sanacora, G., Woolley, J., et al.[2023]

Citations

1. Switzerland pubmed.ncbi.nlm.nih.gov

[Hallucinogenic mushrooms]. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

Psilocybin in neuropsychiatry: a review of its pharmacology, safety, and efficacy. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Psilocybin microdosers demonstrate greater observed improvements in mood and mental health at one month relative to non-microdosing controls. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Dose-response relationships of psilocybin-induced subjective experiences in humans. [2022]

6. Scotland pubmed.ncbi.nlm.nih.gov

The danger of hallucinogenic mushrooms. [2017]

7. United States pubmed.ncbi.nlm.nih.gov

The pharmacology of psilocybin. [2016]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of Escalating Doses of Oral Psilocybin in Healthy Adults. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

The Tolerability and Safety of Psilocybin in Psychiatric and Substance-Dependence Conditions: A Systematic Review. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Role of psilocybin in the treatment of depression. [2020]

11. United States pubmed.ncbi.nlm.nih.gov

DARK Classics in Chemical Neuroscience: Psilocybin. [2019]

12. United States pubmed.ncbi.nlm.nih.gov

Single-Dose Psilocybin Treatment for Major Depressive Disorder: A Randomized Clinical Trial. [2023]