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 explores whether psilocybin, a compound in certain mushrooms, can help people quit smoking. Participants will receive either psilocybin or niacin, a common vitamin, in varying doses across two sessions. The trial aims to determine if psilocybin is more effective than niacin in reducing smoking habits. It suits daily smokers who have tried and failed to quit before and still wish to stop smoking. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to early findings on psilocybin's role in smoking cessation.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Earlier studies have found psilocybin to be safe and potentially helpful for conditions like depression and smoking cessation. Participants usually tolerate it well, with no serious side effects reported in these studies. However, experiences can vary, and some individuals might experience mild to moderate side effects.

Niacin, a type of vitamin B3, is often used in supplements and is considered safe when taken in recommended amounts. Some individuals might experience skin redness and warmth (flushing), itching, or mild stomach upset. Niacin has been used in various health programs, including those aimed at smoking cessation.

Overall, both psilocybin and niacin have been used in humans before, and research shows they are generally well-tolerated. Participants should still consider possible side effects and consult trial coordinators or medical professionals for personalized advice. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard of care for quitting smoking, which often involves nicotine replacement therapies (like patches and gums) or medications such as varenicline and bupropion, psilocybin offers a unique approach by targeting the brain's perception and experience pathways. Psilocybin is a psychedelic compound that is thought to promote significant psychological insights and potentially alter addictive behaviors through profound mystical experiences. Researchers are excited about this treatment because it could provide a new mechanism to help smokers quit by shifting their mindset and breaking the cycle of addiction in a way that traditional medications do not. Niacin, on the other hand, is being explored for its potential to create a flushing response that might enhance the psychological processing of smoking cessation, although its role is less understood compared to psilocybin.

What evidence suggests that this trial's treatments could be effective for quitting smoking?

This trial will compare psilocybin and niacin as treatments for quitting smoking. Research has shown that psilocybin, a substance in magic mushrooms, may help people stop smoking. One study found that participants who took psilocybin had higher success rates in quitting smoking compared to those using regular methods, with some studies showing nearly 30% success after one year. Psilocybin likely works by affecting brain areas related to mood and perception, which might help change smoking habits.

In contrast, niacin, a type of vitamin B3, lacks strong evidence for its use in quitting smoking. While it might help reduce cravings, no substantial proof supports its effectiveness in helping people quit smoking permanently. Niacin is more commonly used for other health benefits, such as improving cholesterol levels. ^{1 4 5 6 7}

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, 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]

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]

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]

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]

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-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]

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]

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]

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]

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]

Citations

1. researchgate.net researchgate.net/publication/289114666_Vitamin_B3_for_Nicotine_Addiction

(PDF) Vitamin B3 for Nicotine Addiction The combination of pharmacotherapy and behavioral interventions, even on a minimal level, have been shown to be effective in cessation.

2. patents.google.com patents.google.com/patent/CA2494743A1/en

CA2494743A1 - Flush niacin used as oral supplementation ... The present invention addresses a vitamin and a method for the cessation of cigarette smoking. The physiological symptoms of nicotine withdrawal can range ...

3. isom.ca isom.ca/wp-content/uploads/2020/01/JOM_2004_19_1_09_Vitamin_B3_for_Nicotine_Addiction.pdf

Vitamin B3 for Nicotine Addiction In most cases, patients con- tinued to smoke, but their cravings for ciga- rettes were considerably reduced and their intakes were roughly halved as a result ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3916028/

three years results of a smoking cessation clinic - PMC Nicotine replacement therapy was found to be more effective at promoting abstinence from smoking than other pharmacologic therapies.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11295357/

Marketing of nicotinamide as nicotine replacement in ... Nicotinamide, also named niacinamide, is a form of vitamin B3 and is commonly used in dietary supplements and medication to treat pellagra, a ...

6. ods.od.nih.gov ods.od.nih.gov/factsheets/Niacin-HealthProfessional/

Niacin - Health Professional Fact Sheet The results also showed that patients taking niacin had an increased risk of ischemic stroke. The authors of two 2017 systematic reviews examining the clinical ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0196064407000741

Toxicity From the Use of Niacin to Beat Urine Drug Screening Niacin (vitamin B3) is promoted for rapidly clearing the body of drugs of abuse, such as cocaine and cannabis, and is alleged to interfere with urine drug ...