Pharmacopsychiatry
July 1, 1998
597 citations
Altered states of consciousness (ASCs) share three core dimensions regardless of how they are induced: Oceanic Boundlessness, Dread of Ego Dissolution, and Visionary Restructuralization. This was shown through 11 experiments with 393 healthy subjects and a field study with 1,133 participants across six countries. The APZ questionnaire, developed to measure these dimensions, shows satisfactory reliability and validity and has become an international standard. A psychometrically improved German version exists, along with the BETA questionnaire for additional dimensions. Versions are available in several languages, with some still untested.
Pharmacopsychiatry
November 1, 2005
198 citations
Two classes of hallucinogenic drugs model different aspects of schizophrenia-like symptoms. In a double-blind crossover study, fifteen healthy volunteers received both the serotonin 5-HT2A agonist DMT and the glutamate NMDA antagonist (S)-ketamine. Nine subjects completed both sessions. DMT produced stronger positive symptoms resembling schizophrenia, such as formal thought disorder and inappropriate affect. (S)-ketamine produced stronger negative symptoms, attention deficits, body perception disturbances, and catatonia-like motor phenomena. The findings suggest neither drug model is overall superior; rather, each models distinct symptom profiles: DMT models paranoid-type psychoses, while (S)-ketamine models psychoses with prominent negative and catatonic features.
Pharmacopsychiatry
December 7, 2020
David E. Nichols, Hannes Walter
131 citations
Interest in psychedelic drugs in psychiatry began in the early 20th century, initially exploring whether mescaline or peyote could produce psychosis-like effects. Over time, researchers focused on whether these effects could illuminate the underlying basis of psychiatric disorders. After LSD's discovery in 1943, interest shifted toward using psychedelics as adjuncts to psychotherapy, which became the primary focus of research through to the present day.
Pharmacopsychiatry
July 1, 1998
F.x. Vollenweider
131 citations
Hallucinogens like LSD and psilocybin, along with dissociative anesthetics such as PCP and ketamine, appear to involve multiple neurotransmitter systems, suggesting a dysbalance between serotonin, glutamate, and dopamine in limbic cortico-striato-thalamic circuitry may be critical for psychotic symptom formation. Using psychometric measures and PET imaging with FDG and specific receptor ligands, the data demonstrate that normal and abnormal thought and behavior are associated with a distributed neuronal network and multiple interactive neurotransmitter systems. The hallucinogen challenge paradigm is a powerful tool for elucidating the pathophysiology of neuropsychiatric disorders.
Pharmacopsychiatry
March 1, 1971
A. A. Kurland, Charles Savage, Walter N. Pahnke et al.
110 citations
A double-blind, controlled study with 135 chronic alcoholics tested whether a high dose of LSD (450 micrograms) as an adjunct to psychotherapy, called psychedelic peak therapy, improved outcomes more than a low dose (50 micrograms). Both groups were treated in a hospital and followed for 18 months. At 6 months, the high-dose group showed a statistically significant advantage in drinking behavior and global adjustment. However, this initial gain faded, and by 12 to 18 months there were no significant differences between groups. Despite this, both groups showed considerably better overall improvement than typical alcoholics in the same setting without LSD-assisted psychotherapy. Further research is needed to sustain initial benefits.
Pharmacopsychiatry
January 25, 2022
W Smallridge, John, X Vollenweider, Franz
107 citations
Psychedelics primarily affect serotonergic receptor subtypes in cortico-thalamic and cortico-cortical feedback circuits, modulating excitatory-inhibitory balance and promoting neuroplasticity in brain structures critical for sensation, cognition, emotions, and self-narrative. Neuroimaging studies link subjective psychedelic experiences and alterations in self-referential processing and emotion regulation to distinct changes in brain activity and connectivity across multiple systems. These findings suggest that changes in self-experience, emotional processing, and social cognition may contribute to the therapeutic potential of psychedelics for psychiatric disorders.
Pharmacopsychiatry
August 4, 2021
Sandeep M Nayak, Natalie Gukasyan, Frederick S Barrett et al.
67 citations
Combining classic psychedelics like LSD or psilocybin with the mood stabilizer lithium carries a high risk of seizures. In an analysis of 62 online reports of such combinations, 47% involved seizures and 18% resulted in bad trips; 39% required medical attention. In contrast, none of 34 reports combining psychedelics with the mood stabilizer lamotrigine involved seizures, and most lamotrigine reports (65%) indicated no effect on the psychedelic experience. The findings suggest that lithium, but not lamotrigine, may pose a significant seizure danger when taken with psychedelics, though further research is needed.
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.
Pharmacopsychiatry
January 20, 2021
Lea J. Mertens, Katrin H. Preller
63 citations
Classical psychedelics such as psilocybin and LSD were studied in the 1950s and 1960s for substance-assisted psychotherapy and are now being reexamined. Modern clinical research provides new evidence for their safety and efficacy in treating substance use disorders and unipolar depression. This review outlines shared pathological mechanisms of these conditions, summarizes current literature on psychedelics' effects, and discusses clinical trials since 2011. Results are promising, but most trials lack methodological rigor for firm conclusions. Larger, blinded, randomized controlled trials with clear patient groups and endpoints are needed. Therapeutic mechanisms remain unknown, and hypotheses from preclinical and human studies require testing.
Pharmacopsychiatry
January 1, 2005
R Bücheler, C H Gleiter, P Schwoerer et al.
63 citations
A mint plant called diviner's sage (Salvia divinorum), used traditionally in Mazatec shamanic ceremonies, is now legally available online. Its active ingredient, salvinorin A, is one of the most potent naturally occurring hallucinogens. Smoking, vaporizing, or chewing the plant induces a short-lived state with intense feelings of depersonalization. The authors report a young man's experience, review the scarce scientific literature, and argue that health professionals should consider Salvia when exploring young people for drug use, as its legal status in most countries and growing appeal among teenagers and young adults in Europe pose public health questions.
Pharmacopsychiatry
April 25, 2017
Norbert Scherbaum, Fabrizio Schifano, Udo Bonnet
46 citations
Hundreds of new psychoactive substances (NPS) have been identified in Europe, mainly synthetic cannabinoids and new synthetic stimulants like cathinones. These are often developed by modifying basic chemical structures such as phenethylamine or tryptamine. Although their pharmacology and toxicology are hardly known, they are sold online as "bath salts" or "incense mixtures" and advertised as "legal highs." Little is known about the prevalence of NPS use, but some molecules may cause severe adverse reactions. Unlike cannabis, synthetic cannabinoid users may experience epileptic seizures, loss of consciousness, and persisting psychopathological disorders. Future studies should inform better-tailored management strategies.
Pharmacopsychiatry
July 1, 1998
Leo Hermle, Euphrosyne Gouzoulis‐mayfrank, Matthew W. Spitzer
44 citations
In 12 healthy men, mescaline triggered an acute psychotomimetic state resembling psychosis, measured by psychiatric scales, and specifically affected visual perception. Neuropsychological tests showed reduced right-hemisphere function, while brain imaging revealed increased frontal lobe activity, especially on the right side, which correlated with the psychotic-like symptoms. These results challenge the idea that reduced frontal lobe activity (hypofrontality) explains acute psychotic symptoms.
Pharmacopsychiatry
January 19, 2022
Hitoshi Sakurai, Kengo Yonezawa, Hideaki Tani et al.
35 citations
Nine antidepressant compounds with mechanisms beyond the monoaminergic hypothesis have shown positive results in phase II or III trials. AXS-05 (dextromethorphan and bupropion) and ansofaxine hydrochloride outperformed placebo in phase III trials for major depressive disorder or treatment-resistant depression. MIJ821, nitrous oxide, psilocybin, ayahuasca, botulinum toxin A facial injection, prasterone, and casopitant each showed at least one positive phase II result. Ayahuasca produced a greater response rate than placebo at one week, suggesting rapid antidepressant effects. These novel compounds may expand treatment options if preliminary findings are confirmed.
Pharmacopsychiatry
May 12, 2021
Gerhard Gründer, Henrik Jungaberle
32 citations
Serotonergic psychedelics like psilocybin, LSD, and DMT, along with MDMA and ketamine, are among the most promising new treatments in psychiatry. Psychedelic-assisted psychotherapy requires redefining psychotherapeutic processes and embedding drug interventions in a new treatment infrastructure. Key challenges for practice and research include informed patient referral, screening, dosing preparation, assisted dosing sessions, psychological integration, and supporting patient communities. Defining treatment delivery infrastructures and therapist training requirements are further challenges. Implementation in routine mental health care must include public communication about the potential and risks. This paper provides a synopsis of challenges for practitioners, researchers, and regulators in the approval processes.
Pharmacopsychiatry
July 1, 1998
K.-A. Kovar
32 citations
Amphetamines, tryptamines, phencyclidines, tetrahydrocannabinol, and ecstasy-group substances are classified as stimulants, hallucinogens, and entactogens. Their effects and mechanisms in different neurotransmitter systems are described. Twenty-eight new compounds in the amphetamine and tryptamine series have been calculated to have hallucinogenic effects exceeding those of mescaline. The distinct metabolic pathways of MDMA (ecstasy) and MDE in humans may account for their individual effects.
Pharmacopsychiatry
November 1, 1971
H Leuner
20 citations
In psycholytic therapy, threshold doses of hallucinogens (LSD-25, psilocybin, CZ-74, and CEY-19) activate unconscious conflict material in a way that is intensely experiential and meaningful for the patient. The drugs' chemical-pharmacological effects can be disregarded beyond their psychoactive role as an adjuvant to the depth-psychological or psychoanalytic process, making this an experimental psychoanalysis. The clinical technique—including patient attunement (set and setting), the type of psychodynamics released, and clinical and statistical results—is detailed, along with indications, contraindications, and risks such as hallucinogen misuse, activation of latent psychosis, and discussed effects on chromosomes.
Pharmacopsychiatry
July 1, 1998
Euphrosyne Gouzoulis‐mayfrank, Frank Schneider, J. Friedrich et al.
16 citations
Hallucinogenic drugs like psilocybin can help identify links between psychological conditions and brain changes seen in both drug-induced and naturally occurring acute psychotic states. This paper discusses methodological considerations for such studies, including subject selection, repeated measures, and control groups. Two example studies are described: one examined psychopathological changes, facial expression, and semantic priming during a psilocybin-induced state; the other compared semantic priming effects after psilocybin, MDE, and d-methamphetamine. Results confirmed time-dependent effects of psilocybin and showed that increased priming effects were restricted to the psilocybin group.
Pharmacopsychiatry
November 1, 1968
R Fischer, Diana Warshay
11 citations
In a sample of 15 college-educated volunteers, a 160 µg/kg dose of psilocybin produced measurable changes in perception and behavior. The degree of drug-induced psychological disturbance, assessed by changes in Minnesota Multiphasic Personality Inventory scores, correlated with greater variability in simple taste and vision tasks. However, the increase in pupil size, a reliable autonomic measure, showed no such relationship. The authors equate the psychological disturbance with each person's symbolic interpretation of their own central nervous system activity.
Pharmacopsychiatry
June 24, 2021
Gerhard Gründer
9 citations
Public press coverage, exemplified by a New York Times front-page article, declares that a psychedelic revolution is approaching and that psychiatry may be transformed. The abstract notes that this renaissance has accelerated over the past year, reflecting growing public and media attention to psychedelics and their potential impact on mental health treatment.
Pharmacopsychiatry
July 30, 2023
Kengo Yonezawa, H. Uchida, T. Yatomi et al.
8 citations
Later age of depression onset is linked to a better treatment response three days after intravenous ketamine in adults with treatment-resistant depression. In a placebo-controlled, double-blind, randomized trial of 31 patients (13 women; average age 48.4 years), logistic regression showed that older age at onset positively correlated with response after three days. No associations were found between response and age, sex, baseline depression severity, or dissociative symptoms. Multiple regression found no factors significantly correlated with change in depression scores. The authors suggest that earlier onset may impair glutamatergic signaling and neuroplasticity, reducing ketamine's effectiveness.
Pharmacopsychiatry
January 1, 1973
Richard M. Hill, Roland Fischer
8 citations
People have a natural tendency to misjudge the position of the visual vertical relative to the gravitational vertical. A 160 µg/kg dose of psilocybin accentuated this misjudgment in 16 college-age volunteers. The drug-induced accentuation was further augmented after exposure to strong body distortion.
Pharmacopsychiatry
November 1, 1969
Peter Gwynne, Roland Fischer, Richard Hill
8 citations
The degree to which a person's perception remains stable across different conditions—with or without psilocybin and during hypnotic induction—appears to be a fixed personality trait. In four subjects classified as either "variable" or "stable" reactors based on their MMPI profiles, those with stable perceptual performance under control conditions also showed stable performance after taking 160–200 µg/kg psilocybin, even when hypnotically induced. Susceptibility to hypnosis did not relate to the ability to exactly replicate the perceptual task under hypnosis.
Pharmacopsychiatry
July 1, 1970
R.M. Hill, R. Fischer
6 citations
Under the influence of psilocybin (160 µg/kg), the abathic plane—the Euclidean visual space—remained relatively stable in 16 volunteers with a median age of 23.5 years, as measured by apparent fronto-parallel plane monitoring. Handwriting area and pressure were also assessed in the same subjects.
Pharmacopsychiatry
January 1, 1975
Roland A. Fischer, Hy Goldman
4 citations
LSD combines structural features of mescaline (a phenylethylamine) and psilocybin (a tryptamine and serotonin analog). Naloxone, which blocks LSD-like side effects of cyclazocine, also blocks effects of LSD, and cross-tolerance may exist between LSD and cyclazocine but not between mescaline and psilocybin. Although LSD binds subcortically, its effect on regional brain perfusion and function is primarily cortical; psilocybin's perfusion shifts are confined to subcortical regions, suggesting other phenylethylamines like mescaline may selectively affect cortical activity.
Pharmacopsychiatry
April 17, 2025
Aleksander Kwaśny, Zuzanna Gaca, Damian Świeczkowski et al.
2 citations
Regulatory compliance in clinical trials of psilocybin for major depressive disorder and treatment-resistant depression shows gaps. A review of four trial protocols from ClinicalTrials.gov found that while they superficially met regulatory requirements, they inadequately addressed drug interactions, concurrent antidepressant use, and prohibited medications. Functional unblinding and expectancy bias were not fully accounted for. Risk mitigation relied on external criteria. Patients with bipolar or schizoaffective disorders were excluded. The most common psilocybin dose studied was 25 mg. Two trials were double-blind. The findings underscore the need for stricter adherence to regulatory standards in psychedelic clinical research and for exploring efficacy in broader populations.