Psychedelic Therapy: A Primer for Primary Care Clinicians-Lysergic Acid Diethylamide (LSD).

BACKGROUND: Lysergic acid diethylamide (LSD) is a hallucinogenic agent. In the mid-20th century, it was used to augment psychoanalysis and to treat alcohol use disorder. However, LSD was banned in 1970 in part because of concerns that it could bring about or exacerbate mental illness. Its therapeutic potential remains incompletely understood. AREAS OF UNCERTAINTY: While uncontrolled recreational use of LSD can, in rare instances, lead to long-term psychosis, adverse events in clinical trials of LSD, such as anxiety, headache, and nausea, have almost always been mild and transient. Serious adverse events, such as intense panic, suicidal ideation, and psychosis, were reported in either none or very few of the participants. However, patient selection criteria, optimal dosing strategy, and appropriate clinical follow-up guidelines remain to be established. THERAPEUTIC ADVANCES: Preliminary data suggest that LSD may be effective for the management of alcohol use disorder, anxiety, and depression. In trials of LSD for treating anxiety and depression associated with life-threatening illnesses, 77% of participants demonstrate durable relief at 1 year post-treatment. Top-line data from a large-scale phase IIb trial (n = 198) indicate that 50% of participants experience remission from generalized anxiety disorder after a single 100 µg dose of LSD. According to a meta-analysis of RCTs on LSD from the mid-20th century, single-dose regimens of LSD significantly improve alcohol use disorder (P < 0.0003) with an odds ratio (OR) of 1.96. LIMITATIONS: Only one large-scale clinical trial (>50 participants) has been conducted on LSD in the contemporary era of psychedelic research. Further studies with large sample sizes are needed to explore potential clinical applications. CONCLUSIONS: Preliminary data suggest that LSD may be one of the most potent treatments for anxiety in patients both with and without a life-threatening illness. LSD may also be beneficial for treating depression and substance use disorders.

Psychedelic-assisted therapy for treating anxiety, depression, and existential distress in people with life-threatening diseases.

BACKGROUND: Psychedelic-assisted therapy refers to a group of therapeutic practices involving psychedelics taken under therapeutic supervision from physicians, psychologists, and others. It has been hypothesised that psychedelic-assisted therapy may reduce symptoms of anxiety, depression, and existential distress in patients facing life-threatening diseases (e.g. cancer). However, these substances are illegal in most countries and have been associated with potential risks. OBJECTIVES: To assess the benefits and harms of psychedelic-assisted therapy compared to placebo or active comparators (e.g. antidepressants) for treatment of anxiety, depression, and existential distress in people with life-threatening diseases. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and two trial registers on 30 March 2024. In addition, we undertook reference checking, citation searching, and contact with study authors to identify additional studies. We used no language or date restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs), with no restrictions regarding comorbidity, sex, or ethnicity. Interventions comprised a substance-induced psychedelic experience preceded by preparatory therapeutic sessions and followed by integrative therapeutic sessions. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. MAIN RESULTS: We included six studies in the review, which evaluated two different interventions: psychedelic-assisted therapy with classical psychedelics (psilocybin ('magic mushrooms') and lysergic acid diethylamide (LSD)), and psychedelic-assisted therapy with 3,4-methylenedioxymethamphetamine (MDMA or 'Ecstasy'). The studies randomised 149 participants with life-threatening diseases and analysed data for 140 of them. The age range of participants was 36 to 64 years. The studies lasted between 6 and 12 months, and were conducted in outpatient settings in the USA and in Switzerland. Drug companies were not involved in study funding, but funding was provided by organisations that promote psychedelic-assisted therapy. Primary outcomes (at 1 to 12 weeks) Anxiety Psychedelic-assisted therapy using classical psychedelics (psilocybin, LSD) may result in a reduction in anxiety when compared to active placebo (or low-dose psychedelic): State Trait Anxiety Inventory (STAI-Trait, scale 20 to 80) mean difference (MD) -8.41, 95% CI -12.92 to -3.89; STAI-State (scale 20 to 80) MD -9.04, 95% CI -13.87 to -4.21; 5 studies, 122 participants; low-certainty evidence. The effect of psychedelic-assisted therapy using MDMA on anxiety, compared to placebo, is very uncertain: STAI-T MD -14.70, 95% CI -29.45 to 0.05; STAI-S MD -16.10, 95% CI -33.03 to 0.83; 1 study, 18 participants; very low certainty evidence. Depression Psychedelic-assisted therapy using classical psychedelics (psilocybin, LSD) may result in a reduction in depression when compared to active placebo (or low-dose psychedelic): Beck Depression Inventory (BDI, scale 0 to 63) MD -4.92, 95% CI -8.97 to -0.87; 4 studies, 112 participants; standardised mean difference (SMD) -0.43, 95% CI -0.79 to -0.06; 5 studies, 122 participants; low-certainty evidence. The effect of psychedelic-assisted therapy using MDMA on depression, compared to placebo, is very uncertain: BDI-II (scale: 0 to 63) MD -6.30, 95% CI -16.93 to 4.33; 1 study, 18 participants; very low certainty evidence. Existential distress Psychedelic-assisted therapy using classical psychedelics (psilocybin, LSD) compared to active placebo (or low-dose psychedelic) may result in a reduction in demoralisation, one of the most common measures of existential distress, but the evidence is very uncertain (Demoralisation Scale, 1 study, 28 participants): post treatment scores, placebo group 39.6 (SEM 3.4), psilocybin group 18.8 (3.6), P ≤ 0.01). Evidence from other measures of existential distress was mixed. Existential distress was not measured in people receiving psychedelic-assisted therapy with MDMA. Secondary outcomes (at 1 to 12 weeks) Quality of life When classical psychedelics were used, one study had inconclusive results and two reported improved quality of life, but the evidence is very uncertain. MDMA did not improve quality of life measures, but the evidence is also very uncertain. Spirituality Participants receiving psychedelic-assisted therapy with classical psychedelics rated their experience as being spiritually significant (2 studies), but the evidence is very uncertain. Spirituality was not assessed in participants receiving MDMA. Adverse events No treatment-related serious adverse events or adverse events grade 3/4 were reported. Common minor to moderate adverse events for classical psychedelics were elevated blood pressure, nausea, anxiety, emotional distress, and psychotic-like symptoms (e.g. pseudo-hallucination where the participant is aware they are hallucinating); for MDMA, common minor to moderate adverse events were anxiety, dry mouth, jaw clenching, and headaches. Symptoms subsided when drug effects wore off or up to one week later. Certainty of the evidence Although all six studies had intended to blind participants, personnel, and assessors, blinding could not be achieved as this is very difficult in studies investigating psychedelics. Using GRADE criteria, we judged the certainty of evidence to be low to very low, mainly due to high risk of bias and imprecision (small sample size). AUTHORS' CONCLUSIONS: Implications for practice Psychedelic-assisted therapy with classical psychedelics (psilocybin, LSD) may be effective for treating anxiety, depression, and possibly existential distress, in people facing a life-threatening disease. Psychedelic-assisted therapy seemed to be well tolerated, with no treatment-emergent serious adverse events reported in the studies included in this review. However, the certainty of evidence is low to very low, which means that we cannot be sure about these results, and they might be changed by future research. At the time of this review (2024), psychedelic drugs are illegal in many countries. Implications for research The risk of bias due to 'unblinding' (participants being aware of which intervention they are receiving) could be reduced by measuring expectation bias, checking blinding has been maintained before cross-over, and using active placebos. More studies with larger sample sizes are needed to reduce imprecision. As the US Drug Enforcement Administration (DEA) currently classifies psychedelics as Schedule I substances (i.e. having no accepted medical use and a high potential for abuse), research involving these drugs is restricted, but is steadily increasing.

New-Onset Seizures in an Adolescent Following Use of LSD while on Low-Dose Lithium Therapy: A Case Study.

This case report presents an occurrence of three generalized seizures within 30 minutes of ingestion of lysergic acid diethylamide (LSD) in a 15-year-old female patient with treatment-resistant depressive disorder recently started on low-dose lithium therapy. She had no personal or family history of seizure, brain injury or other neurological disorder. The patient had a history of monthly LSD use on several occasions in the setting of ongoing fluoxetine and longacting bupropion (Wellbutrin XL) treatment, with seizures occurring only after initiation of lithium. Although the definitive causal link cannot be established, this case report suggests an increased seizure risk with combination of LSD and lithium, even at subtherapeutic serum lithium levels. This case emphasizes the need for further research, careful clinical practice, and patient education regarding the potential dangers of using psychedelic substances with psychopharmacological treatment.

A Critical Appraisal of Evidence on the Efficacy and Safety of Serotonergic Psychedelic Drugs as Emerging Antidepressants: Mind the Evidence Gap.

PURPOSE/BACKGROUND: There has been resurgence of interest in the therapeutic use of serotonergic ("classic") psychedelics in major depressive disorder (MDD) and end-of-life distress. This commentary offers a critical appraisal of current evidence for antidepressant effects of classic psychedelics from contemporary clinical trials and highlights pitfalls that should be addressed before clinical translation. METHODS/PROCEDURES: A narrative review was conducted to identify clinical trials of serotonergic psychedelics for the treatment of MDD and end-of-life distress. Trials published between January 1990 and May 2022 were identified on PubMed using combinations of search terms. FINDINGS/RESULTS: Psilocybin, lysergic acid diethylamide, and ayahuasca have clinical trials to evaluate antidepressant effects. Two studies showed preliminary positive effects of single-dose ayahuasca for treatment-resistant depression. Similar results were seen in lysergic acid diethylamide for end-of-life distress. Small randomized clinical trials (RCTs) of psilocybin combined with psychotherapy showed superiority to waitlist controls and comparable efficacy and safety to an active comparator in MDD, with additional RCTs showing efficacy in end-of-life distress. Adverse events associated with psychedelics were reported as mild and transient. Small homogenous samples, expectancy bias, functional unblinding, and lack of consensus and standardization of psychotherapy are major limitations of all studies. IMPLICATIONS/CONCLUSIONS: Given the methodological limitations of published RCTs, the evidence supporting the efficacy and safety of serotonergic psychedelics for depression is currently of low level. Future research should assess the role of expectancy and psychedelic effects in moderating and mediating treatment response. Innovative trial designs are needed to overcome functional unblinding. For now, psychedelics should remain experimental interventions used within clinical trials.

The potential role of lysergic acid diethylamide for psychological assisted therapy: A meta-analysis of randomised controlled trials in healthy volunteers.

OBJECTIVE: In recent years, interest in using lysergic acid diethylamide (LSD) in psychiatric research and corresponding therapy has increased rapidly. In this meta-analysis, we explored the effects of LSD on healthy subjects with respect to subjective drug effects, blood pressure, heart rate, body temperature and side effects. METHOD: PubMed, Embase, and the Cochrane Library were searched from January 2010 to December 2020 for randomized controlled trials (RCTs) on the effects of LSD in healthy people. Subsequently, 5 RCTs with 132 healthy people which focused on the effects of LSD were enrolled in our study. RESULT: We found that taking 50, 100 and 200 mcg LSD doses were associated with a significant increase in the maximal difference from the baseline compared to the placebo group among the outcomes of AMRS (Adjective Mood Rating Scale) score. Significant differences existed between the LSD and placebo groups when taking 100 and 200 mcg LSD in acute adverse effects (100 mcg: SMD = .97, 95% confidence interval [CI], .50, 1.44, Z = 4.04, p < .001; 200 mcg: SMD = 1.18, 95% CI, 0.65, 1.72, Z = 4.32, p < .001). CONCLUSIONS: Meta-analysis of the subjective effects of LSD in healthy people revealed moderate significant effect sizes in favor of LSD with no significant adverse effects. A 100 mcg dose of LSD has potential for use in psychological-assisted therapy and may improve the mental fitness of patients with disease-related psychiatric distress. Additional clinical trials are necessary to explore the efficacy and safety of LSD as a psychological-assisted therapy.

Post-acute psychological effects of classical serotonergic psychedelics: a systematic review and meta-analysis.

BACKGROUND: Scientific interest in the therapeutic effects of classical psychedelics has increased in the past two decades. The psychological effects of these substances outside the period of acute intoxication have not been fully characterized. This study aimed to: (1) quantify the effects of psilocybin, ayahuasca, and lysergic acid diethylamide (LSD) on psychological outcomes in the post-acute period; (2) test moderators of these effects; and (3) evaluate adverse effects and risk of bias. METHODS: We conducted a systematic review and meta-analysis of experimental studies (single-group pre-post or randomized controlled trials) that involved administration of psilocybin, ayahuasca, or LSD to clinical or non-clinical samples and assessed psychological outcomes ⩾24 h post-administration. Effects were summarized by study design, timepoint, and outcome domain. RESULTS: A total of 34 studies (24 unique samples, n = 549, mean longest follow-up = 55.34 weeks) were included. Classical psychedelics showed significant within-group pre-post and between-group placebo-controlled effects on a range of outcomes including targeted symptoms within psychiatric samples, negative and positive affect-related measures, social outcomes, and existential/spiritual outcomes, with large between-group effect in these domains (Hedges' gs = 0.84 to 1.08). Moderator tests suggest some effects may be larger in clinical samples. Evidence of effects on big five personality traits and mindfulness was weak. There was no evidence of post-acute adverse effects. CONCLUSIONS: High risk of bias in several domains, heterogeneity across studies, and indications of publication bias for some models highlight the need for careful, large-scale, placebo-controlled randomized trials.

Motives and Side-Effects of Microdosing With Psychedelics Among Users.

BACKGROUND: Microdosing with psychedelics has gained considerable media attention where it is portrayed as a performance enhancer, especially popular on the work floor. While reports are in general positive, scientific evidence about potential negative effects is lacking aside from the prevalence and motives for use. The present study addressed this gap by surveying psychedelic users about their experience with microdosing including their dosing schedule, motivation, and potential experienced negative effects. METHODS: An online questionnaire was launched on several websites and fora between March and July 2018. Respondents who had consented, were 18 years of age or older, and had experience with microdosing were included in the analyses. RESULTS: In total, 1116 of the respondents were either currently microdosing (79.5%) or microdosed in the past (20.5%). Lysergic acid diethylamide (10 mcg) and psilocybin (0.5 g) were the most commonly used psychedelics with a microdosing frequency between 2 and 4 times per week. The majority of users, however, were oblivious about the consumed dose. Performance enhancement was the main motive to microdose (37%). The most reported negative effects were of psychological nature and occurred acutely while under the influence. CONCLUSION: In line with media reports and anecdotes, the majority of our respondents microdosed to enhance performance. Negative effects occurred mostly acutely after substance consumption. However, the main reason to have stopped microdosing was that it was not effective. Future experimental placebo-controlled studies are needed to test whether performance enhancement can be quantified and to assess potential negative effects after longer term microdosing.

Twenty percent better with 20 micrograms? A qualitative study of psychedelic microdosing self-rapports and discussions on YouTube.

BACKGROUND: Psychedelic microdosing is the trending practice of using tiny repeated doses of psychedelic substances to facilitate a range of supposed benefits. With only a few published studies to date, the subject is still under-researched, and more knowledge is warranted. Social media and internet discussion forums have played a vital role in the growing visibility of the microdosing phenomenon, and the present study utilized YouTube contents to improve comprehension of the microdosing practice as well as the social interactions and discussions around microdosing. METHODS: Microdosing self-disclosure in YouTube videos and their following comments were qualitatively analyzed by inductive thematic analysis. Various software was utilized to enable gathering and sorting relevant data. RESULTS: Microdosing of psychedelic substances, primarily LSD and psilocybin, was used for therapeutic and enhancement purposes, and predominantly beneficial effects were reported. Many different applications and outcomes were discussed, and therapeutic effects for depression appeared especially noteworthy. Intentions for use were recognized as an influencing factor for the progression and outcomes of microdosing. The function of social interactions was mainly to discuss views on the microdosing phenomenon, strategies for optimal results, minimize risks, and share emotional support. CONCLUSIONS: Potentially, microdosing could provide some of the same benefits (for certain conditions) as full-dose interventions with less risk of adverse reactions related to the sometimes intense experiences of higher doses. Microdosing may well also mean additional benefits, as well as risks, through the repeated exposure over extended periods.

Psychedelic microdosing benefits and challenges: an empirical codebook.

BACKGROUND: Microdosing psychedelics is the practice of consuming very low, sub-hallucinogenic doses of a psychedelic substance, such as lysergic acid diethylamide (LSD) or psilocybin-containing mushrooms. According to media reports, microdosing has grown in popularity, yet the scientific literature contains minimal research on this practice. There has been limited reporting on adverse events associated with microdosing, and the experiences of microdosers in community samples have not been categorized. METHODS: In the present study, we develop a codebook of microdosing benefits and challenges (MDBC) based on the qualitative reports of a real-world sample of 278 microdosers. RESULTS: We describe novel findings, both in terms of beneficial outcomes, such as improved mood (26.6%) and focus (14.8%), and in terms of challenging outcomes, such as physiological discomfort (18.0%) and increased anxiety (6.7%). We also show parallels between benefits and drawbacks and discuss the implications of these results. We probe for substance-dependent differences, finding that psilocybin-only users report the benefits of microdosing were more important than other users report. CONCLUSIONS: These mixed-methods results help summarize and frame the experiences reported by an active microdosing community as high-potential avenues for future scientific research. The MDBC taxonomy reported here informs future research, leveraging participant reports to distil the highest-potential intervention targets so research funding can be efficiently allocated. Microdosing research complements the full-dose literature as clinical treatments are developed and neuropharmacological mechanisms are sought. This framework aims to inform researchers and clinicians as experimental microdosing research begins in earnest in the years to come.

Psychedelic drugs in the treatment of anxiety, depression and addiction. / Psykedeliske stoffer i behandling av angst, depresjon og avhengighet.

BAKGRUNN: Det er økt interesse for psykedeliske stoffer til bruk i behandling av psykiske lidelser. Stoffene regnes som trygge når de gis innenfor en klinisk ramme. Eldre studier fra før 1970 har metodologiske svakheter, men i de senere år har det kommet lovende resultater fra bruk ved unipolar depresjon, depresjon ved livstruende sykdom, angst og avhengighet. Formålet med denne litteraturgjennomgangen er å gi en oversikt over nyere resultater og disse studienes begrensninger. KUNNSKAPSGRUNNLAG: Vi søkte i databasen PubMed etter kliniske studier fra perioden 1990-2017 med søkeordene angst, depresjon, avhengighet og psykedeliske stoffer. Kvaliteten på studiene ble så vurdert ut ifra metode og styrkeberegning. RESULTATER: Søket ga 424 artikler, hvorav ni ble inkludert (fire om angst og depresjon ved livstruende sykdom, to om depresjon, to om avhengighetslidelse og én om tvangslidelse). To dobbeltblinde, randomiserte, kontrollerte fase II-studier med et moderat antall pasienter fant umiddelbar, markert og vedvarende effekt av én enkeltdose psilocybin mot angst og depresjon ved livstruende sykdom. De andre studiene hadde mer usikre resultater. Det var ingen alvorlige bivirkninger eller rapportering om avhengighet. FORTOLKNING: Psykedeliske stoffer i behandling av flere psykiske lidelser har vist lovende resultater, men studiene er små og har metodologiske utfordringer. Det er behov for systematiske kliniske studier for å skaffe solid dokumentasjon for effekt og etablere rutiner for overvåkning av mulige bivirkninger.

Genie in a blotter: A comparative study of LSD and LSD analogues' effects and user profile.

OBJECTIVE: This study aimed to describe self-reported patterns of use and effects of lysergic acid diethylamide (LSD) analogues (AL-LAD, 1P-LSD, and ETH-LAD) and the characteristics of those who use them. METHODS: An anonymous self-selected online survey of people who use drugs (Global Drug Survey 2016; N = 96,894), which measured perceived drug effects of LSD and its analogues. RESULTS: Most LSD analogue users (91%) had also tried LSD. The proportion of U.K. and U.S. respondents reporting LSD analogue use in the last 12 months was higher than for LSD only. LSD analogue users described the effects as psychedelic (93%), over half (55%) obtained it online, and almost all (99%) reported an oral route of administration. The modal duration (8 hr) and time to peak (2 hr) of LSD analogues were not significantly different from LSD. Ratings for pleasurable high, strength of effect, comedown, urge to use more drugs, value for money, and risk of harm following use were significantly lower for LSD analogues compared with LSD. CONCLUSIONS: LSD analogues were reported as similar in time to peak and duration as LSD but weaker in strength, pleasurable high, and comedown. Future studies should seek to replicate these findings with chemical confirmation and dose measurement.

The detection and prevention of unintentional consumption of DOx and 25x-NBOMe at Portugal's Boom Festival.

OBJECTIVE: This paper describes the misrepresentation of LSD at Portugal's Boom Festival 2014 and the prevention of unintentional consumption of DOx and 25x-NBOMe among LSD consumers attending a drug-checking service. METHODS: Two hundred forty-five drug samples expected to contain LSD were submitted to the drug-checking service for chemical analysis. One hundred ten post-test questionnaires were successfully matched with test results. RESULTS: About 67.3% of the alleged LSD samples tested contained only LSD; 0.8% contained LSD combined with adulterants; 24.1% did not contain LSD but did contain another psychoactive substance, including 11.4% that were 2,5-dimethoxyamphetamine derivatives and 9.8% that were N-benzyl-2,5-dimethoxyphenethylamine derivatives; and no psychoactive substance was detected in 7.8%. The majority of service users who received unexpected test results regarding their alleged LSD (74.2%) reported that they did not intend to consume the drug. Following dissemination of alerts on day 2, a larger than expected proportion of all tests conducted were for LSD, when comparing the 2014 festival to 2012, where no such alert was disseminated. CONCLUSIONS: Although these results support the provision of integrated drug-checking services in party settings, evidence of their utility and effectiveness would be improved through future research incorporating more robust measures of outcomes following provision of drug-checking results.

LSD treatment in Scandinavia: emphasizing indications and short-term treatment outcomes of 151 patients in Denmark.

BACKGROUND: New research has suggested the clinical use of lysergic acid diethylamide (LSD) and psilocybin in selected patient populations. However, concerns about the clinical use of LSD were advanced in a large Danish follow-up study that assessed 151 LSD-treated psychiatric patients approximately 25 years after their treatment in the 1960s. AIMS: The purpose of the present study was to give a retrospective account of the short-term outcome of LSD treatment in these 151 Danish psychiatric patients. METHODS: The LSD case material in the Danish State Archives consists of medical case records of 151 LSD-treated patients, who complained and received economic compensation with the LSD Damages Law. The author carefully read and reviewed the LSD case material. RESULTS: LSD was used to treat a wide spectrum of mental disorders. Independent of diagnoses, 52 patients improved, and 48 patients worsened acutely with the LSD treatment. In a subgroup of 82 neurotic patients, the LSD dose-index (number of treatments multiplied by the maximal LSD dose) indicated the risk of acute worsening. In another subgroup of 19 patients with obsessive-compulsive neurosis, five patients later underwent psychosurgery. A small subgroup of 12 patients was treated with psilocybin. The long-term outcome was poor in most of the patients. CONCLUSIONS: Despite the significant limitations to a retrospective design, this database warrants caution in mental health patients. The use of LSD and psilocybin in mental health patients may be associated with serious short- and long-term side effects. Until further trials with rigorous designs have cleared these drugs of their potential harms, their clinical utility in these groups of patients has not been fully clarified.

[Psychoactive effects of 'legal high': About lysergic acid amide (LSA)]. / Effets psychoactifs des « legal high ¼ : à propos de l'acide lysergique amide (LSA).

Lysergic acid amide (LSA) is a natural psychoactive substance consumed as a psychedelic drug. In 2016, 4 cases were reported to the Toulouse Addictovigilance Centre, resulting in unintended psychic effects and led to a hospitalisation in 2 cases. Other cases of serious LSA intoxication are published, including a death. It is important to inform about the risks related to LSA consumption, a substance which is freely available and sometimes hidden behind various plant names.

LSD experiments by the United States Army.

Extensive LSD testing was conducted by the US Army at Edgewood Arsenal and other locations from 1955 to 1967. A number of different reports have been produced describing the health effects of this testing, including the Veterans Health Initiative Report in 2003. By and large, these reports gloss over and minimize the short and long-term side effects and complications of this testing. However, the reports themselves document frequent, severe complications of the LSD. These side effects were regarded by the Army as having been directly caused by the LSD exposure. In view of the current resurgence of interest in hallucinogens within psychiatry, the sanitized version of the effects of LSD exposure on US soldiers needs to be replaced with a more accurate account.

Neurotoxicity and LSD treatment: a follow-up study of 151 patients in Denmark.

LSD was introduced in psychiatry in the 1950s. Between 1960 and 1973, nearly 400 patients were treated with LSD in Denmark. By 1964, one homicide, two suicides and four suicide attempts had been reported. In 1986 the Danish LSD Damages Law was passed after complaints by only one patient. According to the Law, all 154 applicants received financial compensation for LSD-inflicted harm. The Danish State Archives has preserved the case material of 151 of the 154 applicants. Most of the patients suffered from severe side effects of the LSD treatment many years afterwards. In particular, two-thirds of the patients had flashbacks. With the recent interest in LSD therapy, we should consider the neurotoxic potential of LSD.

Schizophrenia and hallucinogen persisting perception disorder: A clinical investigation.

BACKGROUND AND OBJECTIVES: We compared characteristics of schizophrenia patients with prior LSD use who developed hallucinogen persisting perception disorder (SCH+HPPD) with those who did not (SCH-HPPD). METHODS: Data were collected for 37 subjects in the SCH+HPPD group and 43 subjects in the SCH-HPPD group. RESULTS: Socio-demographics and positive symptom scores were similar between groups. Individuals in the SCHIZO+HPPD group scored lower on general psychopathology and negative symptoms scores. DISCUSSION AND CONCLUSIONS: Individuals with schizophrenia and HPPD present with less severe psychopathology, despite persistent perceptual disturbances. SCIENTIFIC SIGNIFICANCE: Our findings highlight the importance of further research into this subset of patients.

Indoleamine Hallucinogens in Cluster Headache: Results of the Clusterbusters Medication Use Survey.

Cluster headache is one of the most debilitating pain syndromes. A significant number of patients are refractory to conventional therapies. The Clusterbusters.org medication use survey sought to characterize the effects of both conventional and alternative medications used in cluster headache. Participants were recruited from cluster headache websites and headache clinics. The final analysis included responses from 496 participants. The survey was modeled after previously published surveys and was available online. Most responses were chosen from a list, though others were free-texted. Conventional abortive and preventative medications were identified and their efficacies agreed with those previously published. The indoleamine hallucinogens, psilocybin, lysergic acid diethylamide, and lysergic acid amide, were comparable to or more efficacious than most conventional medications. These agents were also perceived to shorten/abort a cluster period and bring chronic cluster headache into remission more so than conventional medications. Furthermore, infrequent and non-hallucinogenic doses were reported to be efficacious. Findings provide additional evidence that several indoleamine hallucinogens are rated as effective in treating cluster headache. These data reinforce the need for further investigation of the effects of these and related compounds in cluster headache under experimentally controlled settings.