Psychedelics and Safety

Psychedelics and safety is one of the 'psychedelics and ...' topics that we're currently making a page for. At this moment you can find all papers (in our database) on this topic below.

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Safety Research

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Papers

In our literature study we came across the following studies of note. Browse the meta, review, commentary articles for an overview. Check out the individual studies for specific experiments and observations.

Ethics and ego dissolution: the case of psilocybin

2020 | Sisti, D., Smith, W. R.

This theoretical paper (2020) argues the case for an updated consent process for people undergoing an experience with psilocybin. The paper touches upon the novel risks, the differences with consent for other psychiatric medications, and that between clinical research and mainstream use in psychiatry.

A Public-Health-Based Vision for the Management and Regulation of Psychedelics

2016 | Emerson, B., Haden, M., Tupper, K. W.

This policy article (2016) assesses the harms and benefits of psychedelics use in light of contemporary research and provides a public-health-based model for their regulation, which includes governance, supervision, set and setting controls, youth access, supply control, demand limitation, and evaluation.

MDMA and the “Ecstasy Paradigm”

2014 | Cole, J. C.

This review (2014) examines the lack of evidence to support the notion that MDMA causes widespread cognitive deficits among its users and critiques a prevalent 'ecstasy paradigm' which exaggerates the negative effects of this substance, sustains publication bias by ignoring methodological shortcomings of their study design, and disregarding its therapeutic potential. Although MDMA poses risks to its users, there is no wide-scale evidence to suggest that its users have been damaged, a matter of fact according to the author, which requires no further empiric investigation but a more critical analysis of the already existing evidence.

Psychedelic science in post-COVID-19 psychiatry

2020 | Alexander, L., Baker, A., Brennan, C., Burke, L., Crockett, M. T., Haran, M., Kelly, J. R., O’Keane, V.

This commentary (2020) examines how the COVID-19 pandemic has affected the trajectory of clinical trials investigating psilocybin-treatment for a wide range of conditions, some of which are likely to become even more prevalent in post-COVID-19 clinical psychiatry. Although many of these clinical trials have been temporarily stagnant due to safety measures, ongoing efforts from large scale clinical studies of psilocybin will provide valuable information on its safety, dose optimization, and its efficacy compared to a conventional selective serotonin reuptake inhibitor (SSRI) and additional studies will elucidate whether it is safe to combine them with psilocybin therapy.

Evaluating the Risk of Psilocybin for the Treatment of Bipolar Depression: A Systematic Review of Published Case Studies

2021 | Adams, C., Bradley, E. R., DellaCrosse, M., Gallenstein, M. L., Gard, D. E., Garfinkle, E., Michalak, E. E., Penn, A., Pleet, M. M., Riley, L. S., Woolley, J. D.

This review (2021; pre-print) finds that in the current literature there are some known, but limited, risks of activating mania with psilocybin for those with bipolar depression (BD). The review describes 15 cases of BD and the use of a range of psychedelics.

Risk assessment of ritual use of oral dimethyltryptamine (DMT) and harmala alkaloids

2006 | Gable, R. S.

This relatively early study (2006) combined a literature review with interviews of ceremony participants to establish the effects and toxicity of ayahuasca. The author concludes that risks are relatively low (transient psychological effects, low toxicity, low abuse/addiction potential).

Oral ketamine for the treatment of pain and treatment-resistant depression

2016 | aan Het Rot, R., Balukova, S. M., Chaves, T. V., Kortekaas, R., Schoevers, R. A.

The meta-analysis (2016) examined the antidepressant effects of ketamine in specific regard to its oral administration route. In terms of safety, oral ketamine administration over longer time periods appears to be well-tolerated, but its long-term negative side-effects and the strength of its antidepressant efficacy remain understudied.

Verbal memory impairment in polydrug ecstasy users: a clinical perspective

2016 | de Sousa Fernandes Perna, E. B., Kuypers, K. P. C., Linssen, A., Ramaekers, J. G., Sambeth, A., Schultz, B. G., Theunissen, E. L., van Wel, J. H. P.

This meta-analysis of four placebo-controlled studies (n=130; 2016) investigated the effects of MDMA (75 mg) and history of poly-drug use on verbal memory impairment. Although verbal memory was impaired during acute MDMA intoxication, there was no evidence of memory impairment in relation to either post-acute abstinence or long-term ecstasy use.

Ayahuasca dimethyltryptamine, and psychosis: a systematic review of human studies

2017 | Bouso, J. C., Dos Santos, R. G., Hallak, J. E.

This study (2017) reviews case reports of psychotic episodes occasioned by ayahuasca and DMT. The authors conclude that theses incidences are very rare, but that individuals with a psychotic personal or family history should avoid these substances.

Safety pharmacology of acute MDMA administration in healthy subjects

2017 | Liechti, M. E., Vizeli, P.

This analysis of data from nine double-blind, placebo-controlled studies (n=166) investigated the short-term psychological and physiological safety profile of MDMA (75-125mg) and found that effects were overall positive and risks were low, although adverse effects were more frequent in women than in men.

Compassionate use of psychedelics

2020 | Greif, A., Šurkala, M.

This paper (2020) reviews the safety and efficacy of psilocybin- and MDMA-assisted therapies and argues that it can be rational for some patients to try compassionate psychedelic therapy, notwithstanding the uncertainty of outcomes, as the expected value of psychotherapy can outweigh the expected value of routine care, palliative care, or no care at all. They also address the epistemic risk carried by the notion that psychedelics are philosophically deceptive given that the subjective effects may often feel more real than normal consciousness, but the authors argue that it is not known how classical psychedelics influence one’s beliefs or whether they make one metaphysically irrational, and assert that metaphysics should be ignored in medicine as much as possible. While acknowledging that there are suboptimal uses of psychedelics, the authors see no ethical barriers for their compassionate use in palliative care.

Efficacy and safety of ketamine in bipolar depression: A systematic review

2017 | Alberich, S., González-Pinto, A., López, P., Martínez-Cengotitabengoa, M., Nuñez, N. A., Vieta, E., Zorrilla, I.

This review (2017) compared the safety and efficacy of ketamine for bipolar depression across scientific studies (1 clinical trial, 4 case studies, 5 cohort studies), which showed that symptoms are reduced swiftly and effectively in response to treatment, but they reappear relatively quickly within 3-14 days depending on the scale used to measure symptoms. Ketamine may be considered safe and effective for treating some cases of bipolar depression, although it has a short duration of action, in the absence of confirming studies designed specifically for bipolar depression.

The effects of ecstasy on neurotransmitter systems: a review on the findings of molecular imaging studies

2016 | Booij, J., Reneman, L., Vegting, Y.

This systematic review (2016) examines the acute and long-term neurotoxicity of MDMA across neuroimaging studies that investigated deleterious effects on neurotransmission. MDMA does significantly not affect dopamine transmission, and its effects on the 5-HT2A system remain unclear. Although heavy long-term use was consistently shown to be associated with reduced serotonin binding affinity that may indicate serotonin depletion due to neurotoxicity, abstinence leads to significant recovery. Some studies showed that the use of MDMA is correlated with deficits in several cognitive functions; however, opinions remain divided on this topic.

Ibogaine for treating drug dependence. What is a safe dose?

2016 | Galea, S., Newcombe, D., Schep, L. J., Slaughter, R. J.

This review (2016) argues that the current doses of ibogaine administered as a treatment for drug dependence are too high and should be reconsidered to avoid toxicity and fatalities.

Rapid‐acting antidepressant ketamine, its metabolites and other candidates: A historical overview and future perspective

2019 | Hashimoto, K.

This historic review (2019) examines cellular mechanisms underlying the antidepressant effects of the R(-) and S(+) ketamine enantiomers and their norketamine and hydroxynorketamine metabolites. Although S(+) ketamine exhibits greater affinity to the NMDAR, which is believed to be the mediator of its antidepressant effect, preclinical evidence from animal models suggests that (R)‐ketamine exerts greater potency and longer‐lasting antidepressant effects with less detrimental side‐effects. Given that the phase I clinical studies on R(-)ketamine and hydroxynorketamine are now underway, future studies will be able to perform a direct comparison of their efficacy to treat patients with depression.

Nonanesthetic Effects of Ketamine: A Review Article

2018 | Blaise, G., Eldufani, J., Nekoui, A.

This review (2018) examines (preliminary) evidence of the medical benefits of the non-anesthetic effects of ketamine, as well as supporting evidence of the effectiveness and tolerability of ketamine for improving pain conditions, depression, memory function in Alzheimer's disease, and brain damage after stroke. It also examines underlying mechanisms that exert these effects by stimulating or blocking certain neuroreceptor pathways.

Lysergic acid diethylamide: a drug of ‘use’?

2016 | Barnwal, P., Das, S., Mondal, S., Ramasamy, A., Sen, S.

This review (2016) provides a chronologic history of LSD and examines its safety profile, the potential for abuse, its therapeutic potential to treat alcoholism or terminally ill patients. It also summarizes insights about its receptor pharmacology, mechanism of action, and (adverse) effects, while highlighting some of its potential clinical applications such as an antianxiety agent, a creativity enhancer, a suggestibility enhancer, or a performance enhancer.

Ketamine abuse potential and use disorder

2016 | Lin, D., Liu, Y., Wu, B., Zhou, W.

This review (2016) contrasts the therapeutic potential of ketamine as a fast-acting antidepressant to its potential for substance abuse. It specifically examines the social harms, the psycho-physiological and neurochemical effects, reinforcement mechanisms, and the treatment of ketamine abuse. It concludes that ketamine elicits significant reinforcing and toxic effects, which must be weighed against its antidepressant potential, which needs to be investigated in greater depth.

Meta-analysis of executive functioning in ecstasy/polydrug users

2016 | Jones, A., Montgomery, C., Roberts, C. A.

This meta-analysis (2016) compared cognition between current MDMA (n=1221) users and poly-drug users (n=1224) with regard to executive functions, such as updating, switching, inhibition, and access to long-term memory. Current ecstasy users exhibited significant but small-size deficits in executive functioning, with regard to access to long-term memory, task-switching, and memory updating, which was independent of their accumulated lifetime ecstasy dose.

Classical hallucinogens as antidepressants? A review of pharmacodynamics and putative clinical roles

2014 | Barnes, G., Baumeister, D., Giaroli, G., Tracy, D.

This review (2014) examines the effects of psychedelic drugs with regard to their pharmacodynamics and molecular biology, their electrophysiological and neuroimaging profile, and summarizes the evidence for potential therapeutic mechanisms of action, including effects on neurogenesis, cortical networks, and the immune system. It also examines the clinical profile of psychedelic substances with regard to risks for healthy individuals, as well as the potential to treat clinical conditions such as depression, notwithstanding the criminalized status of psychedelics, despite negligible risk and a lack of evidence for its alleged adverse effects.

Ketamine Users Have High Rates of Psychosis and/or Depression

2015 |

This meta-analysis (n=129) evaluated the relation between long-term treatment with ketamine and the frequency of psychotic and mood disorders, amongst patients located in Hong Kong, China. According to standardized diagnostic criteria, psychosis and/or depression were very common amongst these patients, which raises the issue of safety when considering ketamine for long-term treatment of depression.

The hallucinogenic world of tryptamines: an updated review

2015 | Araújo, A. M., Carvalho, F. M., Carvalho, M., de Lourdes, B. M., de Pinho, P. G.

This review (2015) provides a comprehensive overview of a broad class of serotonergic hallucinogens known as tryptamines, concerning their evolution, prevalence, patterns of use and legal status, chemistry, toxicokinetics, toxicodynamics, and their physiological and toxicological effects on animals and humans. Although classical psychedelics are generally considered to be physiologically safe molecules, there is a lack of information on new tryptamine derivatives, regarding their acute and long-term effects, interactions with other substances, toxicological risk, or addictive potential.

Intranasal drug delivery in neuropsychiatry: focus on intranasal ketamine for refractory depression

2015 | Andrade, C.

This article (2015) examines the advantages and applications of intranasal drug delivery, with a particular focus on the potential of intranasal ketamine for the acute and maintenance therapy of refractory depression. The article contrasts intranasal delivery to oral and sublingual delivery methods, which are less effective with regards to their bioavailability, crossing of the blood-brain-barrier, and rapid onset of drug effects.

Integrating psychotherapy and psychopharmacology: psychedelic-assisted psychotherapy and other combined treatments

2020 | Feduccia, A. A., Garel, N., Greenway, K. T., Jerome, L.

This meta-review (2020) examines the therapeutic frameworks surrounding contemporary practices of psychedelic-assisted psychotherapy, with regard to the historic development of therapeutic models and contemporary insights into extra-pharmacological factors and underlying mechanisms. They highlight that these therapies entail greater environmental sensitivity from the patient's perspective, which requires more meticulous attention for the preparation of the set and setting, a considerably resource-intensive endeavor.

Ketamine for Treatment-Resistant Unipolar and Bipolar Major Depression: Critical Review and Implications for Clinical Practice

2016 | Bobo, W. V., Croarkin, P. E., Frye, M. A., Leung, J. G., Tye, S. J., Vande Voort, J. L.

This review (2016) examines the clinical efficacy of ketamine as fast-acting pharmacotherapy for major depressive disorder and bipolar disorder (BP), in light of the available evidence. In the authors' view, there is insufficient empirical support for the early adoption of ketamine into routine practice, given the lack of data on the longer-term safety of ketamine as an antidepressant therapy, which will require the development of clinical protocols with standardized screening, clinical phenotyping, and follow-up procedures.

Are Psychedelics Something New in Teaching Psychopharmacology?

2020 | Aggarwal, R., Balon, R., Beresin, E. V., Brenner, A. M., Coverdale, J., Guerrero, A. P. S., Louie, A. K., Morreale, M. K.

This editorial paper aims to inform the attitude of medical health professionals towards psychedelics, with regard to evaluating their therapeutic potential in accordance with a rigorous application of the scientific method, while taking social, historical, political, and cultural factors that have influenced their legal status and the discontinuation of prior research.

Flashbacks and HPPD: A Clinical-oriented Concise Review

2014 | Bor, O., Goodman, C., Lerner, A. G., Rudinski, D.

This review (2014) examines the etiology of flashbacks or Hallucinogen Persisting Perception Disorder (HPPD), which represents a cluster of recurrent visual disturbances which have been reported to persist after the acute phase of psychedelic, such as LSD. The authors delineate HPPD type I. disorder that entails short-term, non-distressing, benign, and reversible state accompanied by a pleasant affect, and type II: disorder which entails long-term, distressing, pervasive, either slowly reversible or irreversible, non-benign state accompanied by an unpleasant affect. Although the prevalence of HPPD remains understudied, the authors review a large variety of medications that may alleviate the symptoms of this condition.

How MDMAs Pharmacology and Pharmacokinetics Drive Desired Effects and Harms

2014 | White, C. M.

This review (2014) looks at the desired effects and the possible harms that MDMA can elicit. One could argue that the review in unjustly harsh and implies negative effects not commonly experienced.

Is LSD toxic?

2018 | Grob, C. S., Nichols, D. E.

This study (2018) re-examined five cases of fatality described by media as related to "LSD toxicity," and found that none of those cases were actually attributable to physiological LSD toxicity.

Safety and Side Effects of Ayahuasca in Humans—An Overview Focusing on Developmental Toxicology

2013 | Dos Santos, R. G.

This review (2013) summarizes studies that investigated the toxicity of ayahuasca with regard to its consumption during pregnancy and long-term consumption and did not find evidence indicative of risk. Preclinical studies on rats provide some evidence that select ayahuasca alkaloids may be toxic for development, but these results require further validation through translational research in order to draw conclusions that generalize over human subjects.

Harm potential of magic mushroom use: A review

2011 | Opperhuizen, A., van Amsterdam, J., van den Brink, W.

This review (2011) summarizes the literature on physical or psychological dependence, acute and chronic toxicity, the risk for public health, and criminal aspects related to the consumption of magic mushrooms. The authors conclude that the use of magic mushrooms is relatively safe as only few and relatively mild adverse effects have been reported.

Consumption of Ayahuasca by Children and Pregnant Women: Medical Controversies and Religious Perspectives

2011 | Labate, B. C.

This review (2011) explores common themes and contradictions found between the biomedical, anthropological, and ayahuasca-users' perspectives on the consumption of ayahuasca by children and pregnant women. It raises central issues regarding the limits of freedom of religion and the state's right to interfere in family matters.

Bringing Ayahuasca to the Clinical Research Laboratory

2011 | Barbanoj, M. J., Riba, J.

This commentary article (2005) describes the clinical trials involving the administration of ayahuasca to healthy volunteers at the Autonomous University of Barcelona.

Can MDMA Play a Role in the Treatment of Substance Abuse?

2013 | Jerome, L., Schuster, S., Yazar-Klosinski, B.

This review (2013) evaluates the potential of MDMA to treat substance abuse and dependence. The authors provide evidence that MDMA may have potential as a treatment for these morbidities, but also highlight that classical psychedelics have a better risk:benefit ratio.

Potential Therapeutic Effects of Psilocybin

2017 | Griffiths, R. R., Johnson, M. W.

This review (2017) evaluates the therapeutic research into psilocybin as a treatment for addiction, treatment-resistant depression, and mood and anxiety disorders. The authors also analyse the safety data from these clinical trials.

Hallucinogen persisting perception disorder: what do we know after 50 years?

2003 | Halpern, J. H., Pope Jr, H. G.

This meta-analysis (2003) reviews the findings of 20 studies concerning the diagnosis of Hallucinogen Persisting Perception Disorder (HPPD, or flashbacks) and discusses the difficulty of applying its diagnostic criteria reliably, in light of the ambiguous definition of a 'flashback' and its similarity to other symptoms that are indicative of PTSD. Results conclude that the prevalence of strict HPPD might be very low, while its treatment and etiology remain widely understudied.

Psychedelic 5-methoxy-N,N-dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological actions

2010 | Ai-Ming, Y., Jiang, X. L., Shen, H. W., Winter, J. C.

This review (2010) summarizes recent findings on biotransformation, pharmacokinetics, and pharmacological actions of 5-MeO-DMT, with particular regard to hyper-serotonergic effects of 5-MeO-DMT and bufotenine in response to inhibition of the monoamine oxidase (MAO) metabolic pathway via harmaline (together often found in ayahuasca brews).

Revisiting Wasson’s Soma: Exploring the Effects of Preparation on the Chemistry of Amanita Muscaria

2011 | Feeney, K.

This meta-analysis (n=525) analyzed the effects of Amanita Muscaria (or fly agaric) with regards to inebriation, nausea, and vomiting, sampled across various sources of self-reported ingestion. The dried mushroom caused less nausea and vomiting than when it was consumed fresh, which supports the notion that the preparation methods described for Soma in the Rig Veda may have been a means of reducing the toxicity of Amanita Muscaria, in accordance with Wasson's theory over the identity of Soma.

Health status of ayahuasca users

2012 | Barbosa, P., Bogenschutz, M. P., Mizumoto, S., Strassman, R. J.

This meta-analysis (2012) reviewed the health status of ayahuasca users reported across 10 independent studies, using both quantitative and qualitative analyses. Ayahuasca subjects had similar or better scores than controls and/or the general population on measures of psychiatric morbidity, and psychosocial status, well-being, and consistently less alcohol-related problems, and various subjective (e.g. religious, existential, emotional) benefits.

Do hallucinogens cause residual neuropsychological toxicity?

1999 | Halpern, J. H., Pope Jr, H. G.

This review study (1999) finds few, to none, long-term neuropsychological deficits/toxicity that can be attributed to psychedelic (mainly LSD) use.

A review of emerging therapeutic potential of psychedelic drugs in the treatment of psychiatric illnesses

2020 | Chi, T., Gold, J. A.

This review (2020) presents modern human studies into psychedelic drugs, including psilocybin, LSD, MDMA, and ayahuasca in the treatment of various psychiatric illnesses, including treatment-resistant depression, post-traumatic stress disorder, end-of-life anxiety, and substance use disorders. Safety and efficacy data are also presented, from both human and animal studies.

Ayahuasca and Spiritual Crisis: Liminality as Space for Personal Growth

2008| Lewis, S. E.

This anthropological analysis of phenomenological case reports examines how ayahuasca ceremonies occasion liminal spaces, wherein participants undergo a period of transformation characterized by the process of stripping away one's prior beliefs, identity, and social status, which can also lead to the emergence of spiritual crises. On the basis of a case study within the context of ayahuasca tourism, the authors highlight the need for clinical support to integrate challenging experiences through the exploration of their spiritual and psychological meaning.

Cardiac arrest after ibogaine intoxication

2018| Deyell, M. W., Steinberg, C.

This case study (n=1) documents the cardiotoxicity of the highest survived dose of ibogaine (4.55‐4.9g/70kg) ingested by a 61-year-old man in the context of seeking alternative treatment to overcome a long-standing opioid dependency related to chronic pain. Ibogaine increased heart rate and prolonged the time to recharge heart muscles between beats, and it took 7 days for the patient's heart rhythm to normalize due to the long plasma half-life of the substance. Ibogaine intoxication is therefore a potentially life-threatening scenario due to the cardiotoxic risk of ventricular arrhythmia and requires prolonged cardiac monitoring within a critical care unit.

Ascending single-dose, double-blind, placebo-controlled safety study of noribogaine in opioid-dependent patients

2016| Cape, G., Crockett, R. S., Darpo, B., Devane, J., Friedhoff, L., Glue, P., Harland, S., Howes, J. F., Hung, N., Hung, C. T., Lam, F., Lockhart, M., Tunnicliff, D., Weis, H., Zhou, M.

This randomized, double-blind, placebo-controlled study (n=27) evaluated the safety, tolerability, and pharmacokinetics of noribogaine (60, 120, or 180mg/70kg) administered to opioid-dependent patients withdrawing from methadone. Noribogaine was well tolerated across the entire dose range and a statistically nonsignificant trend toward decreased total score in opioid withdrawal ratings. The ascending noribogaine dose was correlated to prolongation of heart contractions (longer QT intervals) to a degree that would be concerning in a clinical setting, which indicates the need for ECG monitoring to enable dose adjustment or discontinuation to mitigate cardiovascular risk in future studies.

Treatment of acute opioid withdrawal with ibogaine

2009| Alper, K. R., Bastiaans, J., Frenken, G. M. N., Lotsof, H. S., Luciano, D. J.

This series of open-label case studies (n=33) investigated the efficacy of ibogaine (0.42 to 2,03g/70kg) to treat acute withdrawal in patients with opioid dependence. Based on the diagnostic observations of two principal investigators, seventy-six percent of the patients in this series were reportedly free of opioid withdrawal signs and symptoms at 24 hours and did not seek drugs over the period of observation of 72 hours. Observations warrant future investigations to assess the efficacy of ibogaine to treat opioid withdrawal more reliably in controlled clinical studies.

Effects of low dose ibogaine on subjective mood state and psychological performance

2016| Forsyth, B., Garbe, K., Glue, P., Jakobi, H., Jowett, T., Machado, L., Winter, H.

This open-label study investigated the effects of low-dose ibogaine 20mg on subjective mood states and a range of cognitive functions. There was no effect on subjective mood states or cognitive performance related to basic visuomotor function, inhibitory function, memory function, task switching, or selective attention. Future studies would require a wider dose range, placebo-controls, and larger sample sizes to determine whether ibogaine affects these faculties.

Human pharmacology of mephedrone in comparison with MDMA

2016| de la Torre, R., Farré, M., Fonseca, F., Mateus, J., Olesti, E., Papaseit, E., Pérez-Mañá, C., Pujadas, M., Torrens, M.

This randomized, double-blind, crossover, placebo-controlled study (n=12) compared the effects of MDMA (100mg/70kg) and mephedrone (200mg/70kg) with respect to the physiological, subjective, psychomotor, and pharmacokinetic parameters amongst healthy male volunteers. Mephedrone induced stimulant-like effects, which included enhanced euphoria, well-being, feelings of pleasure, and mild changes in perceptions, as well as sympathomimetic effects (hypertension, tachycardia, and mydriasis), but with a faster, less intense, and shorter duration compared to MDMA.

Acute effects of lysergic acid diethylamide on circulating steroid levels in healthy subjects

2016| Dolder, P. C., Kratschmar, D. V., Liechti, M. E., Odermatt, A., Rentsch, K. M., Schmid, Y., Strajhar, P.

This randomized, double‐blind, placebo‐controlled, cross‐over study (n=16) investigated the effects of LSD (200μg) on the plasma concentration-time profiles of steroid levels. LSD induced significant effects on plasma glucocorticoids, including cortisol and particularly corticosterone, which was also closely related to the subjective effects of LSD. The glucocorticoid response to LSD showed no acute pharmacological tolerance, in contrast to the glucocorticoid response to MDMA.

Pharmacokinetics and pharmacodynamics of lysergic acid diethylamide in healthy subjects

2017| Dolder, P. C., Hammann, F., Kraemer, T., Liechti, M. E., Rentsch, K. M., Schmid, Y., Steuer, A. E.

This analysis of data from two double-blind, placebo-controlled studies (n=40) on the pharmacokinetics of LSD (100 and 200µg) found dose-proportional effects. The effects lasted on average 8.2 and 11.6 hours, there was a strong correlation between the blood-plasma level of LSD and subjective effects, but this was only found within-subjects (over time), not between subjects.

Pharmacology of MDMA in humans

2006| Cami, J., de la Torre, R., Farré, M., Lopez, C. H., Mas, M., Menoyo, E., Ortuno, J., Pizarro, N., Roset, P. N., Segura, J.

This paper (2006, n=27) details the physiological effects of MDMA (50-150mg) in humans. There was a slight impairment of psychomotor (e.g. hand eye coordination) performance, higher plasma cortisol and prolactin (both hormones) levels, and (after a decrease in the first hour) an increase in oral/body temperature.

Acute Psychological Adverse Reactions in First-Time Ritual Ayahuasca Users

2021| Alcázar, M. A., Bouso, J. C., Dos Santos, R. G., Gómez-Sousa, M., Hallak, J. E., Jiménez-Garrido, D. F., Ona, G.

This case studies analysis (n=7 of 40 in an earlier study) of data from first-time ayahuasca users still found positive effects after (or even because of) challenging experiences on mental health six months later. An inappropriate setting/context contributed to the challenging experiences.

Psilocin acutely disrupts sleep and affects local but not global sleep homeostasis in laboratory mice

2021| Bannerman, D., Blanco-Duque, C., Breant, B., Goodwin, G. M., Sharp, T., Thomas, C. W., Vyazovskiy, V. V.

This within-subjects animal study (n=8) investigated the effects of psilocin (2 mg/kg; 56mg/28g mouse weight) on the normal sleep-wake cycle and in combination with sleep deprivation. Results indicated that psilocin acutely disrupts sleep, suppressing the maintenance of both NREM and REM sleep, resulting in a pattern of fragmented sleep attempts and frequent brief awakenings which lasted up to 3 hours. No enduring effects of psilocin were observed on sleep-wake quantities, sleep duration, or the recovery from sleep deprivation.

LSD and ketanserin and their impact on the human autonomic nervous system

2021| Olbrich, S., Preller, K. H., Vollenweider, F. X.

This placebo-controlled randomized, crossover study (n=17) investigated the impact of LSD (100 μg) and the counteracting influence of the 5-HT2A receptor antagonist ketanserin (40mg) on the autonomic nervous system within healthy subjects. LSD predominantly increased the sympathetic activity, while ketanserin increased the parasympathetic influence, thus antagonizing the effects of LSD on the autonomic nervous system completely. The magnitude of subjective experiences during the interventions was positively correlated with the sympathetic activity and negatively correlated with the parasympathetic activity, independent of the intervention.

The psychological and physiological effects of MDMA on normal volunteers

1986| Downing, J.

This early study (1986) of the effects of MDMA suggests that MDMA exerts predictable transient psychological effects and shows no major toxicity. However, the author cautiously concludes that the evidence is insufficient to make definitive judgments.

Using the Theory of Planned Behavior to predict implementation of harm reduction strategies among MDMA/ecstasy users

2016| Davis, A. K., Rosenberg, H.

This study (n = 100) used a number of personality variables to predict intention and implementation of harm reduction strategies in MDMA use. The authors found that different variables predicted different strategies.

Psychedelic Harm Reduction and Integration: A Transtheoretical Model for Clinical Practice

2021| Cassidy, K., Gorman, I., Molinar, A., Nielson, E. M., Sabbagh, J.

This paper (2021) introduces the Psychedelic Harm Reduction and Integration approach to working with patients in regards to psychedelics.

Associations between lifetime classic psychedelic use and markers of physical health

2021| Hendricks, P. S., Sexton, J. D., Simonsson, O.

This survey study (2021, n=171,766) aimed to investigate the association between physical health and psychedelic use and found that lifetime psychedelic use was associated with positive physical health markers such as a lower likelihood of obesity. Of course, causality cannot be inferred from these data.

Psilocybin – Summary of knowledge and new perspectives

2013| Horacek, J., Páleníček, T., Tylš, F.

This review (2014) provides a history of psilocybin and a summary of its pharmacology within humans and animals, its psychedelic effects as measured via neuroimaging and psychometric assessments, whilst highlighting its potential for both therapy and abuse.

Dose–response relationships of psilocybin-induced subjective experiences in humans

2021| Hirschfeld, T., Schmidt, T. T.

This meta-analysis (n=349) found that the dose of psilocybin (3-27mg/70kg) correlated positively with positive changes in perception (e.g. ego dissolution). Negative experiences were barely modulated by dose.

Ayahuasca: pharmacology, neuroscience and therapeutic potential

2016| Álvarez, E., de la Fuente Revenga, M., Domínguez-Clavé, E., Elices, M., Feilding, A., Friedlander, P., Pascual, J. C., Riba, J., Soler, J.

This review (2016) examines the pharmacology and neuroscience of ayahuasca, and preliminary findings which indicate the psychological mechanisms associated with its therapeutic benefits are similar to those of mindfulness-based therapy. Ayahuasca appears to enhance self-acceptance and decentering, which converges on evidence from neuroimaging studies that show activation in areas associated with emotional processing and memory formation, thereby enabling individuals to review emotional events with increased vividness and a heightened sense of “reality”. This suggests potential to treat trauma-related conditions and other disorders like borderline personality disorder.

A systematic review of the effects of novel psychoactive substances ‘legal highs’ on people with severe mental illness

2016| Bressington, D., Gray, R., Hughes, E., Ivanecka, A.

This systematic review (2016) examined the available literature on novel psychoactive substances with regard to their effects on people with severe mental illness. Analyses yielded mixed results, given that the people used various different types of substances, or even manifested different types of reactions in response to the same substance in one case with four patients who all had schizophrenia. The review highlights a lack of sufficient empiric evidence on the interaction between psychosis, brain dysfunction, prescribed medication, and novel psychoactive substances to establish adverse effects that are specific to mental illnesses.

A randomized, double-blind, active placebo-controlled study of efficacy, safety, and durability of repeated vs single subanesthetic ketamine for treatment-resistant depression

2020| Albott, C. S., Erbes, C., Lim, K. O., Shiroma, P. R., Thuras, P., Tye, S., Wels, J.

This randomized active placebo-controlled between-subjects study (n=54) compared the antidepressant efficacy of administering six consecutive ketamine infusions (35 mg/70kg) versus consecutive five midazolam infusions (3.15 mg/70kg) followed by a single ketamine infusion, over twelve days. While acute repeated ketamine showed greater antidepressant efficacy to midazolam after five infusions, there was no significant difference in depression scores after the control grouped had received a single ketamine infusion.

Safety of ibogaine administration in detoxification of opioid dependent individuals: a descriptive open-label observational study

2021| Belgers, M., Donders, R., Knuijver, T., Kramers, C., Schellekens, A., van Oosteren, T., Verkes, R. J.

This open-label observational study (n=14) investigated the safety profile of ibogaine (700mg/70kg) for patients with opioid use disorder who were undergoing acute opioid withdrawal. Although patients experienced mild withdrawal symptoms and transient well-tolerated psychomimetic effects, they exhibited abnormal patterns in heart rhythm that constituted an adverse level of cardiovascular risk. This study indicates that even a low-dose administration of ibogaine requires strict cardiac monitoring, and should be restricted to well-controlled settings.

Classic psychedelic coadministration with lithium, but not lamotrigine, is associated with seizures: an analysis of online psychedelic experience reports

2021| Barrett, F. S., Erowid, F., Erowid, E., Griffiths, R. R., Gukasyan, N., Nayak, S.

This analysis of online reports (n=96) found that the use of psychedelics in combination with lithium led to seizures (47%), bad trips (64%), and emergency medical treatment (39%). The authors express the caution people should take when self-medicating/combining psychedelics with antidepressants (with lithium being commonly used for bipolar disorder).

Mania following use of ibogaine: A case series

2015| Koek, R. J., Kopelowicz, A., Marta, C. J., Ryan, W. C.

This case report (n=3) examines patients who developed manic symptoms and diagnosed with Bipolar-I disorder in response to ibogaine use. None of the patients had a prior diagnosis or family history of bipolar disorder, but all of them were poly-drug users or recovering from addiction. Manic symptoms which often included grand delusions that lasted up to two weeks after using ibogaine.

Optimal dosing for psilocybin pharmacotherapy: Considering weight-adjusted and fixed dosing approaches

2021| Barrett, F. S., Carbonaro, T. M., Garcia-Romeu, A., Griffiths, R. R., Johnson, M. W.

This analysis of psilocybin dosages given in 10 previous studies (n=288) found no effect of weight, nor gender, on the effects (acute or long-term) of the dosage (20-30mg) of psilocybin used. The authors recommend a fixed dosing approach going forward to simplify dosing regimes.

A qualitative descriptive analysis of effects of psychedelic phenethylamines and tryptamine

2020| Acosta, P., Palamar, J. J.

This qualitative interview study (n=39) found that within this group about 2/3rds had used 2C drugs (38,5% 2C-B) and compared 2C-B to LSD and MDMA effects, it also compared favorably to other 2C drugs. 4-Aco-DMT was described as mimicking psilocybin.

Switch to mania after ayahuasca consumption in a man with bipolar disorder: a case report

2015| Smith, J. M., Szmulewicz, A. G., Valerio, M. P.

This case report describes the clinical profile of a man from Argentina with a family history of bipolar disorder who participated in a four-day Ayahuasca ceremony that led to the eruption of a hypomanic episode two days after, consisting of mystical and paranoid delusional ideas, auditory hallucinations, racing thoughts, disorganized behavior, elevated energy, and manic euphoria. Given that the remission of psychotic symptoms was immediately followed by an onset of depressive symptoms, the authors theorize that antidepressant effects of harmine may have occasioned the manic shift of his bipolar disorder.

The Potential Dangers of Using MDMA for Psychotherapy

2014| Parrott, A. C.

This review (2014) examines both the negative and positive aspects of using MDMA for psychotherapy, with specific regard to its neurohormonal profile, the effects of serotonergic depletion, and neurotoxicity of repeated usage. The most critical issues are related to the release of difficult feelings and memories and the lack of control thereof due to heightened environmental sensitivity, as well as the risk that negative mood states predominating the phase of neurochemical recovery amongst certain individuals.

Self-Experimentations with Psychedelics Among Mental Health Professionals: LSD in the Former Czechoslovakia

2014| Csémy, L., Winkler, P.

This qualitative study (n=22) conducted a structured interview assessing the attitudes towards psychedelic self-experimentation amongst mental health professionals who took LSD (25-1000μg/70kg) legally between the years 1952–1974 in former Czechoslovakia. Most of the respondents reported positive effects in the domain of self-awareness and/or in their didactic ability to comprehend the world of mentally ill patients. None of the respondents reported any long-term negative effect of their self-experimentation.

Psilocybin dose-dependently causes delayed, transient headaches in healthy volunteers

2012| Griffiths, R. R., Johnson, M. W., Sewell, R. A.

This study (n=18) found that psilocybin frequently caused mild to moderate delayed and transient headaches in healthy volunteers in a dose-dependent manner.

Experienced drug users assess the relative harms and benefits of drugs: a web-based survey

2013| Carhart-Harris, R. L., Nutt, D. J.

This survey study (n=93) investigated the subjective harms and benefits of eleven drugs as reported by experienced drug users. Alcohol and tobacco were ranked as the most harmful, MDMA, LSD, and psilocybin as some of the least harmful drugs.

Residual neurocognitive features of long-term ecstasy users with minimal exposure to other drugs

2011| Gruber, S., Halpern, J. H., Hudson, J. I., Kozin, D., Pope Jr, H. G., Sherwood, A. R.

This field study (n=111) investigated the potential cognitive effects of ecstasy use, improving on previous studies by excluding the use of alcohol or other recreational drugs. The authors found little evidence of decreased cognitive performance in ecstasy users, save for poorer strategic-self-regulation, possibly reflecting increased impulsivity. It was unclear if this was a result of ecstasy use or predisposition in ecstasy users.

In Vivo Imaging of Cerebral Serotonin Transporter and Serotonin 2A Receptor Binding in MDMA and Hallucinogen Users

2011| Christoffersen, M., Erritzoe, D., Frokjaer, V. G., Holst, K. K., Jernigan, T. L., Johansen, S. S., Knudsen, G. M., Madsen, M. K., Ramsøy, T., Rasmussen, P. M., Svarer, C.

This positron emission tomography (PET) study (n=45) assessed the differential effects of MDMA and hallucinogen use on cerebral serotonin transporter (SERT) and serotonin 2A receptor binding. The authors found evidence that MDMA, but not hallucinogen, use is associated with changes in the cerebral presynaptic serotonergic transmitter system.

The administration of psilocybin to healthy, hallucinogen-experienced volunteers in a mock-functional magnetic resonance imaging environment: a preliminary investigation of tolerability

2010| Carhart-Harris, R. L., Feilding, A., Nutt, D. J., Rich, A. S., Sessa, B., Tyacke, R. J., Williams, T. M.

This study (n=9) tested the tolerability of psilocybin in an fMRI environment, and found high levels of tolerability. It found that full-dose psychedelic studies with fMRI equipment are viable.

Does getting high hurt? Characterization of cases of LSD and psilocybin-containing mushroom exposures to national poison centers between 2000 and 2016

2018| Klein-Schwartz, W., Leonard, J. B.

This study (2018) analyzed reports from United States poison centers of individuals presenting with LSD or psilocybin consumption and found that serious adverse effects are rare but possible.

Posttraumatic Stress Disorder After a Psychedelic Experience, a Case Report

2020| Hassan, A. N., Le Foll, B., Rubin-Kahana, D. S.

This study (2020) presents a case report of a man who developed PTSD after an experience with LSD and DMT.

Acute dose of MDMA (75 mg) impairs spatial memory for location but leaves contextual processing of visuospatial information unaffected

2006| Kuypers, K. P. C., Ramaekers, J. G.

This double-blind, placebo-controlled, three-way crossover study (n=18) compared the effects of MDMA (75mg) and Ritalin (20mg) with regard to spatial memory performance. Results indicated that a single dose of MDMA caused subjects to perform worse on a simple spatial memory task only during the acute intoxication, and it did not affect their ability to detect rapid contextual changes in visuospatial information that is relevant for traffic safety.

User perceptions of the benefits and harms of hallucinogenic drug use: A web-based questionnaire study

2010| Carhart-Harris, R. L., Nutt, D. J.

This survey study (n=626) investigated user perceptions of the benefits and harms of using LSD, psilocybin, MDMA, cannabis, ketamine, and alcohol. Overall, LSD and psilocybin were regarded as having the most positive impact on wellbeing, and the least harms in terms of physical and mental health.

Ayahuasca in adolescence: Qualitative results

2011| Alonso, J. N., da Silveira, D. X., de Rios, M. D., Doering-Silveira, E., Grob, C. S., Lopez, E.

This retrospective survey (n=54) investigated the impact of religious Ayahuasca use on adolescents. The qualitative data shows that the teens using Ayahuasca religiously appeared not to differ from their non-ayahuasca-using peers. They were reported to be healthy, thoughtful, considerate, and bonded to their families and religious peers.

Differential tolerance to biological and subjective effects of four closely spaced doses of N,N-dimethyltryptamine in humans

1996| Berg, L. M., Qualls, C .R., Strassman, R. J.

This randomized, double-blind study (n=13) investigated tolerance of repeated doses of 21mg/70kg DMT fumarate in hallucinogen-experienced users. Tolerance to “psychedelic” subjective effects did not occur according to either clinical interview or Hallucinogen Rating Scale scores.

Ayahuasca in adolescence: a preliminary psychiatric assessment

2011| Alonso, J. N., da Silveira, D. X., de Rios, M. D., Doering-Silveira, E., Grob, C. S., Lopez, E., Tacla, C.

This study (n=80) evaluated the psychiatric health of adolescents who used ayahuasca in a religious context, compared to a matched control group of adolescents who did not use ayahuasca. The authors found that, compared to controls, considerable lower frequencies of positive scoring for anxiety, body dysmorphism, and attentional problems were detected among ayahuasca-using adolescents despite overall similar psychopathological profiles.

Daytime ayahuasca administration modulates REM and slow-wave sleep in healthy volunteers

2007| Barbanoj, M. J., Clos, S., Giménez, S., Grasa, E., Riba, J., Romero, S.

This randomized, double-blind, active placebo-controlled, cross-over study (n=22) investigated the effects of daytime ayahuasca (DMT 70mg/70kg) consumption on sleep parameters, compared with active placebo (20mg d-amphetamine). Results showed that daytime serotonergic psychedelic drug administration leads to measurable changes in PSG and sleep power spectrum and suggest an interaction between these drugs and brain circuits modulating REM- and SWS- sleep.

Dose-response study of N,N-dimethyltryptamine in humans: subjective effects and preliminary results of a new rating scale

1994| Kellner, R., Qualls, C .R., Strassman, R. J., Uhlenhuth, E. H.

This randomized, double-blind, placebo-controlled study (n=12) investigated the subjective effects of graded doses of DMT in hallucinogen-experienced users. Effects began almost immediately after DMT administration, peaking at 90 to 120 seconds, and were almost completely resolved by 30 minutes. Hallucinogenic effects were seen after 14 and 21 mg/70kg of DMT, while lower doses, 70 and 35 mg/70kg, were primarily affective and somaesthetic (body + sensory perception).

Acute subjective effects in LSD- and MDMA-assisted psychotherapy

2020| Gasser, P., Liechti, M. E., Oehen, P., Schmid, Y.

This open-label study (n=18) of group-therapy with LSD and MDMA aimed to describe the characteristics, treatment indicators, and acute effects on patients. The study makes a comparison with data from other (earlier) studies on the MEQ and ASC.

Acute effects of lysergic acid diethylamide in healthy subjects

2014| Borgwardt, S., Brenneisen, R., Enzler, F., Gasser, P., Grouzmann, E., Liechti, M. E., Mueller, F., Preller, K. H., Schmid, Y., Vollenweider, F. X.

This double-blind, placebo-controlled study (n=16) described the effects of LSD (200 μg) in healthy subjects. It inhibited prepulse inhibition (startle reflex), increased blood pressure, elicited a positive mood, and had no adverse effect after 72 hours.

Severe Neurological Sequelae after a Recreational Dose of LSD

2020| Aakerøy, R., Ader, T., Andreassen, T. N., Brede, W. R., Frost, J., Krabseth, H. M., Michelsen, L. S., Slettom, G., Slørdal, L., Steihaug, O. M., Stølen, S. B.

This case report highlights that LSD can be dangerous, leading to seizure and brain damage, but this should be read in the context of millions of dosages (of LSD) being taken each year.

Compared

This section compares the research with psychedelics to other therapies, medicines, or treatments.

Measured

This section highlights the various measures used and their use in research.

Researchers

Who are the top researches in this area, the ones who have done the groundbreaking research.

Gaps

What do we not know at this time? Where are the gaps in our knowledge and are we closing it?

Companies

The companies that are actively engaged in researching this topic or (planning to) provide therapy focussed on this topic.

Outside Academia

This section highlights everything done outside of academia, from popular press to books and non academic research.