Nicotine DependenceNCT01943994
Psilocybin-facilitated Smoking Cessation Treatment: A Pilot Study
A study testing Psilocybin-assisted treatment and Nicotine Replacement Therapy (NRT) in people with Nicotine Dependence, run by Johns Hopkins University at 2 sites in United States.
Trial summary
One of the most promising lines of investigation for the therapeutic use of hallucinogens in the 1960s and 1970s was in the treatment of drug dependence. The investigators propose to examine psilocybin administration combined with a structured smoking cessation treatment program in nicotine dependent individuals in… Read more about this study
- Who is it for?
- Ages 21 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Nicotine Dependence
- What is being tested?
- Psilocybin-assisted treatment and Nicotine Replacement Therapy (NRT)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 82 participants
- Where
- 2 sitesUnited States
- Study dates
- Sep 2008to 14 Nov 2023
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 21 to 65 years old.
- Have given written informed consent.
- Have a high school level of education.
- Be a daily smoker with multiple unsuccessful previous quit attempts, and report a continued desire to quit smoking.
- Agree to abstain from smoking and alcohol for 24-hours, and caffeine for 12-hours prior to MRI scanning (for MRI participants only).
- Agree to abstain from smoking for the psilocybin session from 1 hour before psilocybin administration until at least 30 hours afterwards.
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- Agree to consume approximately the same amount of caffeine-containing beverage (e.g., coffee, tea) that he/she consumes on a usual morning, before arriving at the research unit on the morning of drug session day. If the volunteer does not routinely consume caffeinated beverages, he or she must agree not to do so on session day.
- Agree to refrain from using any psychoactive drugs, including alcoholic beverages, within 24 hours of psilocybin administration. Exceptions include caffeine and nicotine.
- Be healthy as determined by screening for medical problems via a personal interview, a medical questionnaire, a physical examination, an electrocardiogram (ECG), and routine medical blood and urinalysis laboratory tests.
Who cannot join
- Women who are pregnant (positive pregnancy test) or nursing, or are not practicing an effective means of birth control
- Cardiovascular conditions: uncontrolled hypertension, angina, a clinically significant ECG abnormality (e.g., atrial fibrilation), TIA in the last 6 months stroke, peripheral or pulmonary vascular disease
- Epilepsy with history of seizures
- Insulin-dependent diabetes; if taking oral hypoglycemic agent, then no history of hypoglycemia
- Currently taking psychoactive prescription medication on a regular basis
- Currently taking on a regular (e.g., daily) basis any medications having a primary centrally-acting pharmacological effect on serotonin neurons or medications that are MAO inhibitors. For individuals who have intermittent or PRN use of such medications, psilocybin sessions will not be conducted until at least 5 half-lives of the agent have elapsed after the last dose.
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- Have HIV or Syphilis.
- Have any current neurological illnesses including, but not limited to, seizure disorders, frequent migraines or on prophylaxis, multiple sclerosis, movement disorders, history of significant head trauma, or CNS tumor.
- Morbidly obese, or severely underweight as determined by medical examination.
- Not suitable to undergo an MRI session due to certain implanted devices (cardiac pacemaker or neurostimulator, some artificial joints, metal pins, surgical clips or other implanted metal parts), body morphology, or claustrophobia (for MRI participants only).
- Current or past history of meeting DSM-IV criteria for Schizophrenia, Psychotic Disorder (unless substance-induced or due to a medical condition), or Bipolar I or II Disorder.
- Current or past history within the last 5 years of meeting DSM-IV criteria for alcohol or drug dependence (excluding caffeine and nicotine) or severe major depression.
- Have a first or second degree relative with schizophrenia, psychotic disorder (unless substance induced or due to a medical condition), or bipolar I or II disorder.
- Currently meets DSM-IV criteria for Dissociative Disorder, Anorexia Nervosa, Bulimia Nervosa, Major Depression, or Post-traumatic Stress Disorder.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Behavioral Pharmacology Research Unit
Baltimore, Maryland, 21224
Neuroimaging Research Branch, NIDA-IRP
Baltimore, Maryland, 21224
About this study
One of the most promising lines of investigation for the therapeutic use of hallucinogens in the 1960s and 1970s was in the treatment of drug dependence. The investigators propose to examine psilocybin administration combined with a structured smoking cessation treatment program in nicotine dependent individuals in order to provide preliminary data on the efficacy of this combined treatment for smoking cessation. Prior work in the investigators laboratory has shown that under carefully prepared and supportive conditions, psilocybin administration can facilitate highly salient experiences with enduring personal meaning and spiritual significance. It is plausible that embedding such highly meaningful experiences into a drug dependence cessation attempt may provide an enduring motivation for remaining abstinent. Cigarette smoking is a good model system for studying drug dependence because users are less likely to be challenged by the many social and economic impairments that often accompany dependence on other drugs such as cocaine, heroin, or alcohol. More specifically, the investigators propose to conduct a randomized controlled comparative efficacy study in which either psilocybin or transdermal nicotine patch are administered under highly supportive conditions to individuals who are nicotine-dependent cigarette smokers, who have had multiple unsuccessful quit attempts, and who continue to desire to quit smoking. Other than nicotine dependence, participants will be healthy. Fifteen participants have already completed a preliminary open-label pilot-study with no control condition. Eighty additional participants will be enrolled and randomized to either psilocybin (n=40), or nicotine patch (n=40) treatment. Participants will receive a 13-week course of cognitive behavioral therapy for smoking cessation, with Target Quit Date set for week 5. After several preparation meetings with study monitors, participants will have either a single day-long psilocybin session using a high dose (30 mg/70 kg), or a standard 8 to 10-week course of nicotine patch treatment. Participant smoking status will be assessed repeatedly for 8 weeks after the Target Quit Date, including biological verification of smoking status through breath and urine samples. Smoking status will also be assessed at three follow up sessions approximately 3, 6, and 12 months after the Target Quit Date. Additionally, 50 of these participants (25 per treatment condition) will undergo MRI scanning before and after Target Quit Date to assess the brain-based mechanisms associated with these treatments. Individuals assigned to the nicotine patch study treatment condition will be eligible to undergo an optional high dose psilocybin session after completing the 6-month follow-up meeting.
- Conditions
- Nicotine Dependence
- Being tested
- Psilocybin-assisted treatment, Nicotine Replacement Therapy (NRT)
- Keywords
- Psilocybin, Smoking cessation
- Medical subject headings
- Tobacco Use Disorder, Smoking Cessation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Psilocybin-assisted treatmentDrug
Also called O-phosphoryl-4-hydroxy-N,N-dimethyltryptamine
Participants will be administered 30 mg/70 kg psilocybin. Preliminary evidence from our ongoing psilocybin dose-effects study suggests that this dose is associated with mystical-type experiences.
Nicotine Replacement Therapy (NRT)Drug
Also called Transdermal Nicotine Patch, Nicoderm CQ
| Study group | Role | What they receive |
|---|---|---|
| Psilocybin-assisted treatment | Experimental | Participants will receive a 13-week cognitive behavioral intervention for smoking cessation, with a high dose of psilocybin (30mg / 70kg) to be administered on the Target Quit Date in week 5. Receives: Drug: Psilocybin-assisted treatment |
| Nicotine Replacement Therapy (NRT) | Active comparator | Participants will receive a 13-week cognitive behavioral intervention for smoking cessation, with a standard 8 to 10-week regimen of NRT to be administered beginning on the Target Quit Date in week 5. NRT for this study will be a transdermal nicotine patch administered according to recommended label usage (For individuals who smoke more than 10 cigarettes per day: 21mg daily weeks 1-6, 14mg daily weeks 7-8, 7mg daily weeks 9-10. For individuals who smoke 10 or less cigarettes per day: 14mg daily for weeks 1-6, 7mg daily for weeks 7-8). Receives: Drug: Nicotine Replacement Therapy (NRT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Prolonged Abstinence: Biologically Verified Cigarette Smoking Abstinence for 6 Months
Cigarette smoking abstinence from the target quit (allowing for an initial 14-day grace period) to the 6-month follow up, as verified by breath carbon monoxide, urine cotinine, and retrospective self-report.
Measured: From the target quit date to the 6-month follow up
Secondary outcomes (2)
Prolonged Abstinence: Biologically Verified Cigarette Smoking Abstinence for 3 Months
Cigarette smoking abstinence from the target quit (allowing for an initial 14-day grace period) to the 3-month follow up, as verified by breath carbon monoxide, urine cotinine, and retrospective self-report.
Measured: From the target quit date to the 3-month follow up
Prolonged Abstinence: Biologically Verified Cigarette Smoking Abstinence for 12 Months
Cigarette smoking abstinence from the target quit (allowing for an initial 14-day grace period) to the 12-month follow up, as verified by breath carbon monoxide, urine cotinine, and retrospective self-report.
Measured: From the target quit date to the 12-month follow up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Sep 2013 (estimated)
- Study startSep 2008
- Primary completion1 May 2023
- Study completion14 Nov 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Nicotine DependenceStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 82 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- Beckley Foundation, Heffter Research Institute
- Responsible party
- Sponsor
- Investigators
- Matthew W Johnson, PhD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01943994
- Sponsor's protocol ID
- NA_00016166
- Status last verified
- May 2025
- First submitted
- 12 Sep 2013
- Last updated
- 25 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Johnson MW, Naude GP, Hendricks PS, Garcia-Romeu A. Psilocybin or Nicotine Patch for Smoking Cessation: A Pilot Randomized Clinical Trial. JAMA Netw Open. 2026 Mar 2;9(3):e260972. doi: 10.1001/jamanetworkopen.2026.0972.
PubMed 41805956
Study at a glance
From the registry record, last updated by the sponsor on 25 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Psilocybin-facilitated Smoking Cessation Treatment: A Pilot Study
- ClinicalTrials.gov ID
- NCT01943994
- Acronym / sponsor ID
- NA_00016166
- Conditions
- Nicotine Dependence
- Keywords
- Psilocybin, Smoking cessation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 82 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- Beckley Foundation, Heffter Research Institute
- Study start
- Sep 2008 (actual)
- Primary completion
- 1 May 2023 (actual)
- Study completion
- 14 Nov 2023 (actual)
- First posted
- 17 Sep 2013 (estimated)
- Results
- Posted 24 Jul 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
One of the most promising lines of investigation for the therapeutic use of hallucinogens in the 1960s and 1970s was in the treatment of drug dependence. The investigators propose to examine psilocybin administration combined with a structured smoking cessation treatment program in nicotine dependent individuals in order to provide preliminary data on the efficacy of this combined treatment for smoking cessation. Prior work in the investigators laboratory has shown that under carefully prepared and supportive conditions, psilocybin administration can facilitate highly salient experiences with enduring personal meaning and spiritual significance. It is plausible that embedding such highly meaningful experiences into a drug dependence cessation attempt may provide an enduring motivation for remaining abstinent. Cigarette smoking is a good model system for studying drug dependence because users are less likely to be challenged by the many social and economic impairments that often accompany dependence on other drugs such as cocaine, heroin, or alcohol. More specifically, the investigators propose to conduct a randomized controlled comparative efficacy study in which either psilocybin or transdermal nicotine patch are administered under highly supportive conditions to individuals who are nicotine-dependent cigarette smokers, who have had multiple unsuccessful quit attempts, and who continue to desire to quit smoking. Other than nicotine dependence, participants will be healthy. Fifteen participants have already completed a preliminary open-label pilot-study with no control condition. Eighty additional participants will be enrolled and randomized to either psilocybin (n=40), or nicotine patch (n=40) treatment. Participants will receive a 13-week course of cognitive behavioral therapy for smoking cessation, with Target Quit Date set for week 5. After several preparation meetings with study monitors, participants will have either a single day-long psilocybin session using a high dose (30 mg/70 kg), or a standard 8 to 10-week course of nicotine patch treatment. Participant smoking status will be assessed repeatedly for 8 weeks after the Target Quit Date, including biological verification of smoking status through breath and urine samples. Smoking status will also be assessed at three follow up sessions approximately 3, 6, and 12 months after the Target Quit Date. Additionally, 50 of these participants (25 per treatment condition) will undergo MRI scanning before and after Target Quit Date to assess the brain-based mechanisms associated with these treatments. Individuals assigned to the nicotine patch study treatment condition will be eligible to undergo an optional high dose psilocybin session after completing the 6-month follow-up meeting.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Psilocybin-assisted treatment | Experimental | Drug: Psilocybin-assisted treatmentParticipants will receive a 13-week cognitive behavioral intervention for smoking cessation, with a high dose of psilocybin (30mg / 70kg) to be administered on the Target Quit Date in week 5. |
| Nicotine Replacement Therapy (NRT) | Active comparator | Drug: Nicotine Replacement Therapy (NRT)Participants will receive a 13-week cognitive behavioral intervention for smoking cessation, with a standard 8 to 10-week regimen of NRT to be administered beginning on the Target Quit Date in week 5. NRT for this study will be a transdermal nicotine patch administered according to recommended label usage (For individuals who smoke more than 10 cigarettes per day: 21mg daily weeks 1-6, 14mg daily weeks 7-8, 7mg daily weeks 9-10. For individuals who smoke 10 or less cigarettes per day: 14mg daily for weeks 1-6, 7mg daily for weeks 7-8). |
Who may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 21 to 65 years old.
- Have given written informed consent.
- Have a high school level of education.
- Be a daily smoker with multiple unsuccessful previous quit attempts, and report a continued desire to quit smoking.
- Agree to abstain from smoking and alcohol for 24-hours, and caffeine for 12-hours prior to MRI scanning (for MRI participants only).
Key exclusion criteria (14 listed)
- Women who are pregnant (positive pregnancy test) or nursing, or are not practicing an effective means of birth control
- Cardiovascular conditions: uncontrolled hypertension, angina, a clinically significant ECG abnormality (e.g., atrial fibrilation), TIA in the last 6 months stroke, peripheral or pulmonary vascular disease
- Epilepsy with history of seizures
- Insulin-dependent diabetes; if taking oral hypoglycemic agent, then no history of hypoglycemia
- Currently taking psychoactive prescription medication on a regular basis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Psilocybin-assisted treatmentAlso: O-phosphoryl-4-hydroxy-N,N-dimethyltryptamineParticipants will be administered 30 mg/70 kg psilocybin. Preliminary evidence from our ongoing psilocybin dose-effects study suggests that this dose is associated with mystical-type experiences. | Drug | Psilocybin-assisted treatment |
| Nicotine Replacement Therapy (NRT)Also: Transdermal Nicotine Patch, Nicoderm CQ | Drug | Nicotine Replacement Therapy (NRT) |
Primary outcome
Prolonged Abstinence: Biologically Verified Cigarette Smoking Abstinence for 6 Months
Time frame: From the target quit date to the 6-month follow up
Cigarette smoking abstinence from the target quit (allowing for an initial 14-day grace period) to the 6-month follow up, as verified by breath carbon monoxide, urine cotinine, and retrospective self-report.
2 secondary outcomes
Prolonged Abstinence: Biologically Verified Cigarette Smoking Abstinence for 3 Months
Time frame: From the target quit date to the 3-month follow up
Prolonged Abstinence: Biologically Verified Cigarette Smoking Abstinence for 12 Months
Time frame: From the target quit date to the 12-month follow up
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41805956Johnson MW, Naude GP, Hendricks PS, Garcia-Romeu A. Psilocybin or Nicotine Patch for Smoking Cessation: A Pilot Randomized Clinical Trial. JAMA Netw Open. 2026 Mar 2;9(3):e260972. doi: 10.1001/jamanetworkopen.2026.0972.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Matthew W Johnson, PhD principal investigator
Johns Hopkins University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Psilocybin-assisted treatment and Nicotine Replacement Therapy (NRT) in people with Nicotine Dependence, run by Johns Hopkins University at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Prolonged Abstinence: Biologically Verified Cigarette Smoking Abstinence for 6 Months (time frame: From the target quit date to the 6-month follow up). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01943994, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 May 2025.