Psychopharmacology
December 1, 2011
Roland R Griffiths, Matthew W Johnson, William A Richards et al.
938 citations
Psilocybin can produce mystical-type experiences that lead to lasting positive changes in attitudes, mood, and behavior. In a double-blind study, 18 adults (17 with no prior hallucinogen use) received 0, 5, 10, 20, or 30 mg/70 kg psilocybin in five sessions under supportive conditions. At the two highest doses, 72% of volunteers reported a mystical-type experience, and 39% experienced extreme anxiety or fear. One month later, participants rated these sessions as having substantial personal and spiritual significance, with the ascending dose sequence showing greater positive effects. At 14 months, these positive ratings remained undiminished and were consistent with observer reports. The effects generally increased with dose.
Journal of Psychopharmacology
September 28, 2011
Katherine A Maclean, Matthew W Johnson, Roland R Griffiths
907 citations
Core personality traits are generally stable after age 30, but a high dose of the hallucinogen psilocybin can increase Openness to experience in healthy adults. In a double-blind controlled study, participants who had a mystical experience during their psilocybin session showed significantly higher Openness than baseline, and this increase persisted for more than a year. The findings suggest that psilocybin and mystical-type experiences can produce lasting personality change in adults.
Journal of Psychopharmacology
October 6, 2015
Frederick S Barrett, Matthew W Johnson, Roland R Griffiths
634 citations
The 30-item revised Mystical Experience Questionnaire (MEQ30) is validated using data from five controlled laboratory experiments with psilocybin. Participants (n=184) received a moderate to high oral dose of psilocybin (at least 20 mg/70 kg). Confirmatory factor analysis shows the MEQ30 is reliable and internally valid. Structural equation models demonstrate external and convergent validity: latent variable scores on the MEQ30 positively predict persisting changes in attitudes, behavior, and well-being attributed to psilocybin experiences, beyond the participant-rated intensity of drug effects. The findings support the MEQ30 as an efficient measure of individual mystical experiences. A method to score a "complete mystical experience" from previous versions is validated, and a stand-alone MEQ30 is provided.
Pharmacology & therapeutics
May 1, 2019
Matthew W Johnson, Peter S Hendricks, Frederick S Barrett et al.
520 citations
Classic psychedelics like LSD, mescaline, and psilocybin are serotonin 2A receptor agonists with a long history of sacramental use and a resurgence in research. Epidemiological studies suggest naturalistic nonmedical use may be linked to positive mental health and prosocial outcomes, though some individuals are harmed in unsupervised settings. Recent therapeutic studies indicate efficacy in treating psychological distress from life-threatening diseases, depression, and nicotine and alcohol addictions. These compounds fairly reliably occasion mystical experiences, which are associated with improved psychological outcomes in healthy volunteers and patients. Neuroimaging studies reveal neurobiological mechanisms, broadening understanding of the brain, serotonin system, and consciousness. Overall, classic psychedelics show strong therapeutic potential and as tools for investigating mystical experiences and brain function.
Journal of psychopharmacology (Oxford, England)
March 1, 2015
Peter S Hendricks, Christopher B Thorne, C Brendan Clark et al.
377 citations
Among over 190,000 US adults surveyed from 2008 to 2012, those who had ever used classic psychedelics (such as LSD or psilocybin) showed lower odds of past-month psychological distress, past-year suicidal thinking, past-year suicidal planning, and past-year suicide attempt compared with those who had not. The reduced odds ranged from 14% lower for suicidal thinking to 36% lower for suicide attempt. In contrast, use of other illicit drugs was generally linked to higher odds of these outcomes. The findings suggest that classic psychedelics might help prevent suicide and that their strict legal status should be reconsidered to allow more research.
Journal of Psychopharmacology
May 14, 2019
Albert Garcia-Romeu, Alan K Davis, Fire Erowid et al.
286 citations
In a survey of 343 people who had problematic alcohol use for an average of seven years and then used psychedelics in non-clinical settings, 83% no longer met criteria for alcohol use disorder after the experience. Most respondents were White males in the USA who took moderate or high doses of LSD or psilocybin. They rated the experience as highly meaningful and insightful, and 28% said changes in life priorities or values helped reduce alcohol misuse. Greater dose, insight, mystical-type effects, and personal meaning were linked to larger reductions in drinking. The results suggest naturalistic psychedelic use may reduce problematic alcohol use, supporting further research into psychedelic-assisted treatment.
Journal of psychopharmacology (Oxford, England)
September 1, 2020
Alan K Davis, John M Clifton, Eric G Weaver et al.
144 citations
Inhaling N,N-dimethyltryptamine (DMT) can trigger encounters with seemingly autonomous entities. A survey of 2,561 people (average age 32, 77% male) found that these encounters primarily involve visual and extrasensory perception, such as telepathy. Entities are most often described as beings, guides, spirits, aliens, or helpers. Although 41% of respondents felt fear, the dominant emotions were love, kindness, and joy, both in the respondent and attributed to the entity. Most believed the entity was conscious, intelligent, and benevolent, existing in a real but different dimension. 69% received a message, and 19% a prediction. Over half of those who were atheist before no longer identified as atheist afterward.
Psychopharmacology
February 1, 2018
Theresa M Carbonaro, Matthew W Johnson, Ethan Hurwitz et al.
139 citations
Psilocybin and dextromethorphan (DXM) both produce powerful subjective effects, but their experiences differ profoundly. In a double-blind comparison with 20 participants, high doses of both drugs caused similar overall drug effect strength and time-course. Psilocybin uniquely fostered richer, more complex visual experiences—including more movement, brightness, and kaleidoscopic imagery—along with greater mystical-type and psychologically insightful experiences and deeper music absorption. DXM, by contrast, produced stronger feelings of disembodiment, nausea, and light-headedness. Both drugs increased blood pressure, heart rate, and pupil dilation while impairing motor performance and balance.
Psychopharmacology
March 1, 2013
Katherine A Maclean, Matthew W Johnson, Chad J Reissig et al.
134 citations
Inhaled salvinorin A, the active compound in Salvia divinorum, produces intense, dose-related subjective and cognitive effects that peak within 2 minutes and rapidly dissipate. In eight healthy adults with hallucinogen experience, high doses frequently caused maximal drug strength ratings or unresponsiveness. The compound induced dissociative effects and impaired recall and recognition memory, with some overlap with classic hallucinogens but a qualitatively distinct profile. No persisting adverse effects were observed at one-month follow-up. These findings contribute to understanding the kappa opioid system and may inform future therapeutic applications.
Drug and alcohol dependence
May 1, 2011
Matthew W Johnson, Katherine A Maclean, Chad J Reissig et al.
134 citations
Salvinorin A, the psychoactive compound in Salvia divinorum, produces rapid, dose-dependent subjective effects that peak at 2 minutes and subside within 20 minutes after inhalation. In a double-blind, placebo-controlled study with 4 healthy hallucinogen-using adults, doses from 0.375 to 21 μg/kg increased ratings of mystical-type experiences and effects similar to classic hallucinogens. Salvinorin A did not significantly raise heart rate or blood pressure. Participants reported intense experiences involving altered spatial orientation, pressure on the body, childhood memories, cartoon-like imagery, and contact with entities. The findings suggest salvinorin A has a unique profile that includes mystical-type effects.
Drug and alcohol dependence
June 1, 2012
Matthew W Johnson, R Andrew Sewell, Roland R Griffiths
121 citations
Psilocybin frequently causes headache in a dose-dependent manner, with incidence, duration, and severity increasing at higher doses. In a double-blind study with 18 healthy participants given 0, 5, 10, 20, or 30 mg/70 kg of psilocybin, all headaches had delayed onset, were transient, and lasted no more than a day. Headaches were neither severe nor disabling. Possible mechanisms include nitric oxide release. These findings indicate headache is an expected adverse event in both nonmedical use and human research, but should not hinder future psilocybin research.
Psychopharmacology
October 1, 2018
Frederick S Barrett, Theresa M Carbonaro, Ethan Hurwitz et al.
109 citations
Classic psychedelics and dissociative hallucinogens may share some neuropsychological effects despite different pharmacology. In a double-blind, placebo-controlled study, 20 hallucinogen users received 10, 20, and 30 mg/70 kg psilocybin, 400 mg/70 kg dextromethorphan (DXM), and placebo across five sessions. Neither drug caused global cognitive impairment. Psilocybin produced dose-dependent effects on psychomotor performance, working memory, episodic memory, associative learning, and visual perception. DXM affected psychomotor performance, visual perception, and associative learning similarly to moderate-to-high psilocybin doses. Psilocybin affected working memory more than DXM, while DXM had greater effects on balance, episodic memory, response inhibition, and executive control.
Journal of Psychopharmacology
September 1, 2015
Peter S Hendricks, Matthew W Johnson, Roland R Griffiths
107 citations
Adults in the United States who had ever used psilocybin alone showed lower odds of past-month psychological distress (weighted OR = .81) and past-year suicidal thinking, planning, and attempt compared with those who had never used any classic psychedelic. Those who used psilocybin without other psychedelics also had reduced odds of psychological distress relative to users of other classic psychedelics. The findings suggest psilocybin may have therapeutic potential and a favorable safety profile, but do not directly address clinical applications or risk.
Personality and individual differences
October 15, 2017
Frederick S Barrett, Matthew W Johnson, Roland R Griffiths
98 citations
People who score higher on neuroticism (or lower on emotional stability) tend to report more intense challenging experiences, such as fear, grief, and paranoia, during psilocybin sessions. Data from two online surveys with 1,993 and 981 participants showed that scores on the Challenging Experience Questionnaire were negatively associated with emotional stability in the first study and positively associated with neuroticism in the second. The findings suggest that personality traits, particularly neuroticism, may help explain why some individuals have more difficult “bad trips” with classic hallucinogens like psilocybin.
Psychopharmacology
September 1, 2012
Chad J Reissig, Lawrence P Carter, Matthew W Johnson et al.
89 citations
High doses of the cough suppressant dextromethorphan (DXM) produce perceptual changes, mystical-type experiences, and physiological effects similar to those of classic hallucinogens like psilocybin. In a double-blind study, 12 healthy volunteers with histories of hallucinogen use received single oral doses of DXM ranging from 100 to 800 mg/70 kg, triazolam, or placebo. DXM dose-dependently increased blood pressure, heart rate, and emesis, and elicited observer-rated hallucinogen-like effects such as visual distortions and joy. After 400 mg/70 kg DXM, 11 of 12 participants thought they had received a classic hallucinogen. At a 1-month follow-up, volunteers reported lasting positive changes in spirituality, attitudes, and mood attributed to the session.
Journal of psychopharmacology (Oxford, England)
March 1, 2022
Anna O Ermakova, Fiona Dunbar, James Rucker et al.
83 citations
5-MeO-DMT is a short-acting psychedelic tryptamine found in nature and used historically for spiritual purposes. This review of existing literature covers its pharmacology, chemistry, metabolism, epidemiological studies, and reported effects. 5-MeO-DMT acts as a serotonergic agonist with highest affinity for 5-HT1A receptors. Animal model studies exist, but human clinical studies are lacking. Epidemiological data indicate it induces profound alterations in consciousness, including mystical experiences, with potential beneficial long-term effects on mental health and well-being. Its short duration, relative lack of visual effects, and higher rates of ego-dissolution make it a potentially useful addition to the psychedelic pharmacopoeia, warranting further clinical exploration with appropriate precautions.
Pharmacopsychiatry
July 1, 2021
Sandeep Nayak, Matthew W Johnson
66 citations
Psychedelic therapy shares key features with conventional psychotherapy, such as relying on subjective experiences that produce lasting change. This review examines how psychedelic drugs may amplify standard therapeutic processes, especially through effects on meaning and relationship, while also introducing unique elements. The authors propose a framework explaining why psychedelics can be effective across diverse psychotherapy modalities. They also review formal psychotherapies used in modern psychedelic trials and discuss implications for clinical ethics and trial design. The goal is to provide a common conceptual vocabulary for understanding therapeutic psychedelic effects beyond any single treatment approach.
Psychopharmacology
August 1, 2020
Theresa M Carbonaro, Matthew W Johnson, Roland R Griffiths
51 citations
Psilocybin produces stronger positive subjective effects than dextromethorphan (DXM) at comparable peak drug strength, which may explain its higher rates of non-medical use. In a double-blind study of 20 healthy participants with hallucinogen experience, psilocybin (10, 20, 30 mg/70 kg) and DXM (400 mg/70 kg) both increased ratings of overall drug effect, but psilocybin showed dose-related increases in nine domains linked to reinforcing effects—including liking, visual effects, positive mood, insight, social effects, appreciation of beauty, awe, meaningfulness, and mystical experience. For most ratings, the two highest psilocybin doses were significantly greater than DXM, and DXM never exceeded psilocybin. These differences matched participants' desire to take the drug again.
Drug and alcohol dependence
March 1, 2013
Lawrence P Carter, Chad J Reissig, Matthew W Johnson et al.
28 citations
Acute high doses of dextromethorphan (DXM) impair attention, working memory, episodic memory, and metacognition in healthy volunteers with histories of hallucinogen use. Impairments from 100–300 mg/70 kg DXM were generally smaller than those from 0.5 mg/70 kg triazolam. Doses needed to match triazolam's impairment exceeded 10–30 times the therapeutic dose. Supratherapeutic doses caused impairments on all tasks, indicating a broad therapeutic window for over-the-counter DXM when used appropriately, but relevance to high-dose abuse.
Adolescent psychiatry (Hilversum, Netherlands)
April 1, 2013
Ryan Vandrey, Matthew W Johnson, Patrick S Johnson et al.
26 citations
Over the past decade, non-medical use of novel drugs—including synthetic cannabinoids, synthetic cathinones, and the hallucinogen Salvia divinorum—has proliferated worldwide, sold over the counter and online as legal highs or substitutes for traditional illicit drugs. These substances, often first synthesized in academic or pharmaceutical labs, are not detected in routine drug screens and lack substance-specific treatments for toxicity. The review describes their epidemiology, toxicologic and pharmacological properties, and characteristic signs of misuse, recommending that clinicians use a symptom-specific treatment approach for each case.
JAMA psychiatry
January 1, 2023
Brian D Kiluk, Bethea A Kleykamp, Sandra D Comer et al.
22 citations
A review sponsored by a public-private partnership addresses clinical trial design for new opioid use disorder (OUD) treatments that target systems other than the μ-opioid receptor. The authors present consensus recommendations for evaluating novel therapies such as cannabinoids, psychedelics, sedative-hypnotics, and immunotherapeutics. Key design elements include specifying the treatment stage (e.g., early abstinence, long-term recovery), defining the treatment's role (adjunctive or independent), selecting patient-informed primary outcomes that assess opioid use patterns, retention, and quality of life, and monitoring adverse events like relapse or overdose, especially when patients are not on maintenance opioid agonist or antagonist medications. Incorporating input from people with lived experience is urged to accelerate development and uptake of effective therapeutics.
Psychedelic medicine (New Rochelle, N.Y.)
March 1, 2024
Justin C Strickland, Albert Garcia-Romeu, Matthew W Johnson
20 citations
Brief four- and seven-item versions of the Mystical Experience Questionnaire (MEQ-4) and Challenging Effects Questionnaire (CEQ-7) show strong correspondence with the full 30- and 26-item scales. In a sample of 1,160 individuals who used psychedelics therapeutically outside research settings, total scores for the brief versus full versions correlated at r = 0.89 for the MEQ and r = 0.90 for the CEQ. Classic psychedelics like LSD and psilocybin produced higher scores on both brief and full versions than MDMA. Higher mystical experience scores on both versions were linked to greater reductions in depression and anxiety, while challenging experiences showed limited association with mental health changes. The brief scales substantially reduce participant burden while maintaining validity.
Advances in pharmacology (San Diego, Calif.)
January 1, 2022
Justin C Strickland, Matthew W Johnson
13 citations
The past decade has seen rapid growth in research on the basic science and clinical understanding of psychedelics. This chapter reviews the human behavioral pharmacology of three classic psychedelics: psilocybin, LSD, and DMT. It covers historical background, drug classification, and special considerations such as set and setting, mystical experience measurement, blinding, placebos, and abuse liability. The subjective, physiological, and clinical effects of these substances are described, documenting a unique collection of acute and long-term behavioral changes. Clinical research shows potential therapeutic utility in difficult-to-treat conditions like treatment-resistant depression, alcohol use disorder, and cigarette smoking. Future work is needed to reveal mechanisms of behavior change.
Pharmacological research
January 1, 2024
David B Yaden, Andrea P Berghella, Peter S Hendricks et al.
12 citations
Classic psychedelic-assisted therapies show initial promise for treating substance use disorders (SUDs) and may become legally available options. This article describes how these therapies could fit within current evidence-based SUD treatments, suggesting broad compatibility with most mainstream clinical approaches.
Journal of psychopharmacology (Oxford, England)
April 1, 2016
Matthew W Johnson, Katherine A Maclean, Michael J Caspers et al.
11 citations
After inhaling a high dose of vaporized salvinorin A (18–21 mcg/kg), plasma levels of the compound peak at 2 minutes and then rapidly decline. Higher drug levels are strongly linked to stronger subjective and observer-rated drug effects. Prolactin rises significantly from 5 minutes onward, peaking at 15 minutes, while cortisol increases are inconsistent across participants. Hormonal changes do not closely track drug levels. This work demonstrates a direct relationship between salvinorin A plasma concentrations and drug effects in humans, validating an efficient inhalation method.