Psychoactive Substances for Hallucinations

Overseen By Zach Daily

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Johns Hopkins University

Must not be taking: MAO inhibitors, Serotonin agents

Disqualifiers: Pregnancy, Cardiovascular conditions, Epilepsy, others

Compensation: Varies

Number of Visits: 15

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore whether various psychoactive substances can produce experiences similar to those of traditional psychedelics. Participants will try up to six different substances, including psilocybin, ketamine, and MDMA, and report their effects. The trial seeks healthy and psychologically stable adults who can maintain their usual caffeine intake and avoid other drugs around the testing days.

As a Phase 1 trial, this research focuses on understanding how these substances work in people, offering participants the unique opportunity to be among the first to experience these treatments.

Will I have to stop taking my current medications?

You may need to stop taking certain medications, especially those that affect serotonin or are MAO inhibitors, before participating in the trial. If you take these medications occasionally, you must wait until they are fully out of your system before starting the sessions. Nonprescription medications and supplements need approval from the study investigators.

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

Research has shown that the substances tested in this trial—psilocybin, ketamine, DMT, MDMA, DXM, and THC—have some safety data available.

Studies indicate that psilocybin can alter perception and sense of time, but it is usually well-tolerated in controlled settings. It is known for creating euphoric and spiritual experiences with few physical risks.

Ketamine, used as an anesthetic, can cause feelings of detachment from reality. It might raise blood pressure and heart rate and cause headaches, especially at higher doses.

DMT can cause strong visual and auditory hallucinations. While generally safe in controlled environments, it can sometimes lead to frightening experiences.

MDMA, often called ecstasy, is known for boosting mood and empathy, but it can also increase heart rate and cause dehydration.

DXM, found in some cough syrups, can cause hallucinations and euphoria at high doses, but it is considered safe when used under supervision.

THC, the active ingredient in cannabis, is generally safe but can cause mild side effects like dizziness or anxiety in some people.

While these substances have different effects, they are generally well-tolerated in controlled settings, such as clinical trials. Safety remains a key focus, especially in early trials where researchers carefully monitor any adverse effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using psychoactive substances like psilocybin, ketamine, DXM, DMT, MDMA, and THC for hallucinations because these treatments work differently than traditional antipsychotic medications. Unlike standard antipsychotics, which mainly target dopamine receptors to reduce symptoms, these substances interact with a broader range of neurotransmitter systems, potentially offering new pathways to manage hallucinations. Psilocybin, for example, affects serotonin receptors, which might help in altering perception and mood more effectively. Additionally, these substances might offer rapid effects, which contrasts with the weeks it often takes for traditional medications to show results. This could mean quicker relief for patients experiencing distressing hallucinations.

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

This trial will compare the effects of various psychoactive substances on hallucinations, including psilocybin, ketamine, dextromethorphan (DXM), dimethyltryptamine (DMT), methylenedioxymethamphetamine (MDMA), and tetrahydrocannabinol (THC). Studies have shown that psilocybin can quickly and lastingly improve mood, reducing anxiety and depression. Research indicates that ketamine also provides fast relief from severe depression, with its mind-altering effects possibly contributing to its benefits. Dextromethorphan, a common ingredient in cough syrup, can alter perception and cause effects similar to other hallucinogens. Dimethyltryptamine (DMT) is known for causing strong visual hallucinations and has shown potential for quickly improving depression symptoms. Methylenedioxymethamphetamine (MDMA) increases feelings of closeness and empathy, and early evidence suggests it can effectively treat PTSD. Tetrahydrocannabinol (THC), the main component in cannabis, affects mood and perception but may worsen psychotic symptoms in some people. Participants in this trial may receive any of these substances or a placebo during the experimental sessions. ^{6 7 8 9 10}

Who Is on the Research Team?

Frederick Barrett, Ph.D.

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

This trial is for individuals who are medically and psychiatrically healthy, as determined by exams, interviews, and questionnaires. Participants will undergo up to 6 sessions receiving different psychoactive substances or a placebo without knowing which they're getting.

Inclusion Criteria

Agree to refrain from using any psychoactive drugs, including alcoholic beverages, within 24 hours of each drug administration. Exceptions include daily use of caffeine and nicotine

I am healthy and mentally stable, confirmed by medical tests.

BMI between 18 and 34 kg/m2

Exclusion Criteria

History of meeting DSM-5 criteria for moderate or severe substance use disorder (excluding tobacco), requiring that at least one of the endorsed criteria relates to prior loss of control of substance use

I have diabetes and use insulin without experiencing low blood sugar.

Psychiatric disorder that in the clinical opinion of the study team would put the participant at an especially high risk for adverse effects from the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Preparation

Participants complete 2 preparation sessions before the first experimental session

1 week

2 visits (in-person)

Experimental Sessions

Participants complete up to 6 experimental drug administration sessions with psychoactive substances or placebo

6 weeks

6 visits (in-person)

Follow-up

Participants are monitored and debriefed after each session to discuss subjective experiences

2 weeks

6 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Dextromethorphan (DXM)
• Dimethyltryptamine (DMT)
• Ketamine
• Methylenedioxymethamphetamine (MDMA)
• Psilocybin
• Tetrahydrocannabinol (THC)

Trial Overview The study tests the effects of Dextromethorphan (DXM), Dimethyltryptamine (DMT), Ketamine, MDMA, THC, Psilocybin versus a placebo in producing psychedelic experiences. It's double-blind with randomized drug assignments and includes preparation and follow-up discussions.

How Is the Trial Designed?

Group I: Other psychoactive drugs Experimental Treatment 5 Interventions

Participants may receive varying oral psychoactive doses of ketamine, dextromethorphan (DXM), N,N-dimethyltryptamine (DMT), 3,4-methylenedioxymethamphetamine (MDMA), or delta-9-tetrahydrocannabinol (THC). All dose levels will be limited to doses that have been safely administered within a single day in a laboratory context in the past.

Group II: Psilocybin Active Control 1 Intervention

Participants may receive varying oral psychoactive doses of psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine)

Group III: Placebo Placebo Group 1 Intervention

Participants may receive an inactive placebo during any one of the experimental sessions.

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Published Research Related to This Trial

Dextromethorphan (DM), an over-the-counter cough medicine, has been linked to substance dependence and can induce severe psychiatric effects, including psychosis and withdrawal symptoms, particularly when abused at high doses.

The active metabolite of DM, dextrorphan (DOR), exhibits properties similar to dissociative drugs and may contribute to addiction and life-threatening complications, highlighting the need for greater awareness among healthcare providers regarding its abuse potential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dextromethorphan psychosis, dependence and physical withdrawal. Miller, SC.[2022]

In a study involving 20 hallucinogen users, neither psilocybin nor dextromethorphan (DXM) caused global cognitive impairment, indicating a safety profile for both substances during peak effects.

Psilocybin showed greater improvements in working memory compared to DXM, while DXM had stronger effects on balance and executive control, suggesting that these two hallucinogens may have different neuropsychological profiles despite their shared hallucinogenic properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-blind comparison of the two hallucinogens psilocybin and dextromethorphan: effects on cognition. Barrett, FS., Carbonaro, TM., Hurwitz, E., et al.[2019]

Five teenage males died after intentionally consuming large doses of dextromethorphan, an over-the-counter cough suppressant, highlighting the drug's potential for severe toxicity when misused.

Postmortem analyses revealed dextromethorphan levels far exceeding therapeutic ranges, with concentrations linked to known cases of abuse, leading to legal actions against those involved in its distribution.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five deaths resulting from abuse of dextromethorphan sold over the internet. Logan, BK., Goldfogel, G., Hamilton, R., et al.[2019]

Dextromethorphan (DXM), commonly found in over-the-counter cold and cough medications, can cause severe psychological effects when taken in excessive amounts, a practice known as 'robotripping.'

This misuse of DXM can lead to a manic toxidrome characterized by symptoms such as psychomotor agitation, hallucinations, and paranoia, highlighting potential risks associated with recreational use, especially among young users.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mania after misuse of dextromethorphan: a case report and brief review of "robotripping". Stanciu, CN., Penders, TM.[2015]

A study involving 20 healthy participants found that psilocybin produced stronger subjective effects compared to dextromethorphan (DXM), particularly in areas like positive mood, visual effects, and feelings of awe, which may explain its higher rates of non-medical use.

Both drugs showed significant effects compared to placebo, but psilocybin's effects increased with higher doses, while DXM did not surpass psilocybin in any measure, indicating that psilocybin may have more reinforcing properties that encourage its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subjective features of the psilocybin experience that may account for its self-administration by humans: a double-blind comparison of psilocybin and dextromethorphan. Carbonaro, TM., Johnson, MW., Griffiths, RR.[2023]

A healthy 30-year-old male experienced significant auditory and visual hallucinations after inhaling 25 mg of vaporized THC, indicating that cannabis can produce hallucinogenic effects under certain conditions.

The hallucinations reported were distinct from those typically associated with classic hallucinogens, suggesting that cannabis may have a unique mechanism of action that warrants consideration in its clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

"Hallucinations" Following Acute Cannabis Dosing: A Case Report and Comparison to Other Hallucinogenic Drugs. Barrett, FS., Schlienz, NJ., Lembeck, N., et al.[2020]

In a study involving 20 healthy participants, psilocybin (at doses of 10, 20, and 30 mg/70 kg) produced significantly greater visual effects and mystical experiences compared to dextromethorphan (DXM at 400 mg/70 kg), indicating its unique efficacy in inducing profound psychological insights.

Both psilocybin and DXM increased physiological responses like heart rate and blood pressure, but DXM was associated with more negative effects such as disembodiment and nausea, suggesting that while both drugs have hallucinogenic properties, their safety profiles and subjective experiences differ significantly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-blind comparison of the two hallucinogens psilocybin and dextromethorphan: similarities and differences in subjective experiences. Carbonaro, TM., Johnson, MW., Hurwitz, E., et al.[2019]

Dextromethorphan (DXM) is a widely used cough suppressant that is generally safe and effective at recommended doses, but it can lead to severe psychosis when abused at high doses (over 1500 mg/day).

A case study of a 40-year-old woman with DXM use disorder highlighted that her psychotic symptoms only resolved after treatment with an antipsychotic and mood stabilizer, emphasizing the need for clinicians to recognize the psychiatric risks associated with recreational DXM use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dextromethorphan in Cough Syrup: The Poor Man's Psychosis. Martinak, B., Bolis, RA., Black, JR., et al.[2019]

Psychedelic substances like psilocybin, DMT, LSD, and MDMA are being researched for their potential therapeutic effects on psychiatric disorders, which are a leading cause of global disability.

The review highlights ongoing and recently completed clinical trials, indicating a renewed interest in the safety and efficacy of these compounds, especially in combination with psychotherapeutic approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psychedelic renaissance: Revitalized potential therapies for psychiatric disorders. Rhee, TG., Davoudian, PA., Sanacora, G., et al.[2023]

A study of 108 blood samples from suspected impaired drivers revealed that dextromethorphan concentrations were significantly higher than therapeutic levels, with the highest levels found in young males aged 16-20, indicating potential abuse.

Drivers under the influence of dextromethorphan showed impaired psychomotor performance and signs of central nervous system depression, suggesting serious safety concerns related to its misuse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dextromethorphan in Wisconsin drivers. Cochems, A., Harding, P., Liddicoat, L.[2019]

Persistent visual illusions can occur for over 12 months after excessive cannabis use, as seen in two patients who experienced symptoms like vibrations and impaired depth perception.

In a third patient, who had a history of LSD use, visual hallucinations re-emerged 20 years after stopping drugs, triggered by factors like alcohol intake, indicating that long-term effects of these substances can lead to lasting cortical dysfunction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Persisting visual hallucinations and illusions in previously drug-addicted patients. Gaillard, MC., Borruat, FX.[2013]

Large doses of dimethylacetamide have been identified as a potent hallucinogenic drug in humans, indicating its significant psychoactive effects.

The study observed characteristic changes in electroencephalographic activity, suggesting that dimethylacetamide alters brain function during its hallucinogenic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dimethylacetamide: a hitherto unrecognized hallucinogenic agent. WEISS, AJ., MANCALL, EL., KOLTES, JA., et al.[2019]

Hallucinogenic drugs, such as LSD and PCP, can produce significant effects at non-toxic doses, with each type affecting the brain's neurotransmitter systems differently, leading to unique behavioral outcomes.

Management of patients experiencing hallucinogenic intoxication requires careful assessment of symptoms to differentiate between drug effects and other medical or psychiatric conditions, with treatment options including benzodiazepines for panic reactions and antipsychotics for severe cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical features and management of intoxication due to hallucinogenic drugs. Leikin, JB., Krantz, AJ., Zell-Kanter, M., et al.[2019]

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