Lsd trial

Dosage, frequency and duration of the treatment, for both experimental and control interventions were extracted. For non-pharmacological comparators, type, frequency and duration of the intervention were extracted, if appropriate. As studies with different diagnostic groups were included, outcomes varied depending on the psychiatric condition under study. In any case, change scores from baseline or endpoint were extracted.

Side effects and overall tolerability were also studied. Randomized controlled trials of LSD as a therapeutic tool for psychiatry were included. This review included only randomized controlled clinical trials involving patients with a diagnosis of mental illness.

Experimental studies in healthy volunteers were excluded. Trials with no control group or not randomized, animal studies, observational studies, review papers, qualitative studies, case reports, opinion pieces or comments, letters or editorials, conference abstract, posters and books chapters were excluded. Of interest were interventions using LSD, as a stand-alone treatment or as an adjunctive treatment.

Only studies comparing LSD with other interventions were included. Active and non-active comparators were included. The Cochrane Collaboration risk of bias assessment tool was used to determine the quality of the studies This tool involves an assessment of six specific domains: 1 sequence generation, 2 allocation concealment, 3 blinding of participants, 4 personnel and outcome assessors, 5 incomplete outcome data, and 6 selective outcome reporting and other sources of bias.

The tool was applied to each RCT independently by two authors. Discrepancies were resolved through discussion with a third author. A total of 3, papers were identified through the search in Pubmed, and 12 additional records were found through other sources manual search based on review papers and meta-analysis. After the removal of duplicates and exclusion based on titles or abstracts, 43 papers were screened in more detail for eligibility. Subsequently, another 32 were excluded, which resulted in the 11 papers used in this systematic review.

The quality of the great majority of the clinical trials found did not conform to modern standards, with a non-randomized control group or without control group itself. The highest quality of trials was observed in studies on the therapeutic use of LSD in alcoholism. The detailed description of all studies included and their main results can be found in Tables 1 and 2.

Tables 1 and 2 show these clinical trials ordered by date of publication. Note the important year interval between the study by 63 ; and the modern study by Gasser et al. A summary of risk of bias is presented in Table 3. Based on the definitions provided by the Cochrane risk of bias assessment tool 67 , no trials were assessed to show a high risk of bias related to sequence generation, and all trials used random assignment. Moreover, all trials attempted to conceal allocation, but most of them were judged to have unclear risk of allocation concealment 63 , 65 , 69 , 71 — 73 because did not describe methods in detail.

Five trials 59 , 70 , 71 , 73 , 74 were judged to have a high risk of bias due to blinding of patients or staff. In two of them 59 , 70 , treatment allocation was concealed only until the time of the possible LSD session, and in the other three trials 71 , 73 , 74 no attempt of blindness or to single blind was made or designed.

All trials were judged to have low or an unclear risk of bias due to independent and blind assessment. In one trial 72 the outcome assessor was not explicitly described as allocation-blind and in another one 59 the assessment was collected by self-report questionnaire, confirmed by telephone interview with a close relative or friend. The rest of them 62 , 65 , 68 — 71 , 74 , 75 had independent and allocation-blind assessors.

Two trials 62 , 72 were judged to have a high risk of bias due to incomplete outcome data, because participants were excluded if they did not complete the intended treatment program 72 or if received additional doses of LSD Four studies 59 , 65 , 69 , 73 had substantial rates of missing participants at follow-up. However, retention rates were generally high, and data missed in one of the trials 63 was only representative at 12 and 18 months, not at 6 months.

In the other three trials 59 , 69 , 73 , authors considered missing participants as unimproved. Three trials 69 , 70 , 73 were judged to have a high risk of bias because of possible selective outcome reporting, presenting lack of clarity at short-term follow-up clinical outcome and giving more detailed data at medium or late-term follow-up. Another trial 71 was judged to have an unclear risk because some measures were not strictly reported.

Finally, four trials 62 , 65 , 71 , 74 were judged to have a high risk of other sources of bias. In one of them 62 , due to baseline imbalance full-dose LSD participants were less likely to be divorced and more likely to have prior admissions for alcohol treatment , other trial 65 due to treatment time full-dose LSD participants were more likely to have more psychotherapy hours and the rest of them 71 , 74 due to a shorter time of hospitalization [from one day 71 to a few days 74 ] for the LSD treatment group and not the control group.

Two last trials 73 , 75 presented unclear risk of bias due to uneven concurrent use of other pharmacological treatments during study between participants. LSD was administered to patients in a dose range from 20 to mcg. The oral route was significantly the most used one, while one study 71 used the intravenous route and another one 68 did not describe the route used. A single dose of LSD was the procedure of choice for most selected clinical trials.

Other studies 71 , 73 opted for a dosage-escalation approach, and some 73 , 75 offered the possibility of repeating LSD doses at 2—3 week intervals. The concomitant use in some of the studies of other pharmacological principles, such as dextroamphetamine 73 prior to the dose of LSD, or chlorpromazine or promazine 71 , 73 after LSD treatment is worth mentioning.

Since the therapeutic potential of LSD may be underestimated or masked by such treatments. Most studies describe exclusion criteria for patients to be treated with LSD. Severe organic disease mainly at neurological and cardiovascular levels was a common exclusion criteria 63 , 66 — Two of the studies 67 , 75 also excluded those patients with a history of severe affective disorder.

Most clinical trials 65 , 68 — 71 , 74 , 75 discarded those patients with active psychosis for the study, but some of them 65 , 68 , 70 , 74 did not rule out patients with a history of psychosis in the past. It is noteworthy that in the study of Tomsovic and Edwards 59 , LSD was administered to a subgroup of 12 patients diagnosed with schizophrenia withdrawn from Table 1 , due to modern exclusion criteria , to which they applied a separate statistical analysis that showed better results for the subgroup of non- schizophrenics who had received a single LSD dose.

Two cases of serious adverse effects were reported. In one of the studies 69 , authors described a tonic—clonic seizure, without subsequent complications, in a patient with a previous history of seizures in a context of abstinent clinical symptoms. In another one 74 , a case of prolonged psychosis was reported in a year-old patient with a previous history of recurrent psychotic episodes in the context of hospitalization during adolescence.

This patient received psychotherapy and antipsychotic medication, recovering without later complications. No other serious adverse effects were described in the remaining subjects. Five studies within our review 68 , 70 — 73 designed a control group for which no drug was administered, and three others 59 , 65 , 76 had a control group in which the usual treatment was applied to patients during hospitalization. Most studies see Table 1 had a control group in which active placebo was used, and four of them 62 , 65 , 72 , 75 used LSD itself at a lower dose.

The difficulty in maintaining patient and therapist uncertainty, even with active placebo, is underlined by authors. With ephedrine sulfate 68 , in 19 of 20 cases the therapist correctly guessed which type of drug was administered to the patient, and 20 mcg of LSD 75 was considered too low a dose to avoid unmasking the control group, both for patient and therapist.

There was great heterogeneity among the clinical trials chosen for this review in terms of patient preparation and the general therapeutic program to which LSD treatment was added. Table 2 shows the type of treatment program used in each study, ranging from 24 h to 90 days from the start of treatment to patient discharge. The treatment program between different studies also differed in structure, varying between highly structured intensive programs 70 with five weekly meetings, seminars, group and individual therapy, occupational therapy and rehabilitation program and the absence 73 of a specific program.

Preparation of the subject for LSD treatment ranged from very brief orientation 68 — 71 to extensive preparation 62 , 65 , 74 , 75 with the aim of promoting the therapeutic experience.

Preparation time pre-LSD session, Table 2 , ranged from a few hours to 5 weeks. The only information provided to subjects in some cases was the great variation in the individual response of the drug 68 , or very brief data on the nature of response 69 , with no intention to perform previous therapy. One of these authors 70 points out that the previous preparation of patients to LSD administration was possibly insufficient for achieving therapeutic objectives.

In the earliest study meeting these characteristics 72 , patients were previously informed of the nature of the drug, stating whether they would receive a small or a large dose. Within the LSD group of treatment full-dose or active placebo , approximately half of the patients performed the session during the first 3 weeks, with the remaining subjects receiving LSD treatment during the last 3 weeks.

Again, great heterogeneity was observed among studies regarding the therapeutic approach during the treatment with LSD. Two studies 68 , 71 applied an approach based on active and directed interviews focused on problems derived from alcohol dependence.

In one of these trials 68 , these interviews were described as an attempt to discover alternatives to alcohol use, and to define patient attitudes regarding the transfer with the therapist, the act of moving towards drinking, parental relationships, suicidal ideation or sexual behavior. In three of the studies 59 , 69 , 72 , no psychotherapy attempts were made during the treatment session.

In one of them 69 , an effort was made to maintain a supportive environment, which included non-verbal communication. Regarding the physical sensory stimuli and interpersonal environment of subjects during the LSD treatment see Table 2 , in five trials 59 , 62 , 69 , 72 , 75 , musical stimulation during the session was offered.

In four of the studies 65 , 70 , 73 , 74 , the physical environment was not described. Likewise, in two studies 66 , 69 , the use of waist belt to bed method was mentioned to prevent subjects from leaving their position. Regarding the interpersonal environment, the fact that in the earliest study 68 subjects were unaccompanied for an indefinite period of time during the treatment is noteworthy. The efficacy of the intervention with LSD was presented by the main diagnosis where the substance was administered.

Most clinical trials in this review 59 , 62 , 68 — 73 evaluated the therapeutic potential of LSD in the treatment of alcohol use disorder. The main outcomes of these studies and their main statistical analysis were summarized below, by order of publication.

There were no significant differences between groups either in the Drinking History Questionnaire nor in number of voluntary contacts with the clinic afterwards. In summary, it was observed a significant effect of LSD in four studies performed. However, this effect was related to quality of life and general health in some of the studies, with no clear improvements in alcohol abstinence.

Two trials 65 , 73 evaluated LSD as a treatment of neurotic symptoms. This diagnosis was referred to as depressive neurosis, obsessive-compulsive reaction, phobic reaction, anxiety state, hysteria, psychoneurosis with somatic symptoms, character disorder and sexual neurosis.

The presence of all symptomatology was not required, and a subset of neurotic symptoms was adequate. Only one study 74 met the inclusion criteria in our review. A modern study 75 assessed anxiety associated with chronic inflammatory disease, chronic motor disease and cancer.

In some studies 69 , 73 patients could be discharged after 24 h or in less time 73 if they were able to be assisted by friends or relatives.

Other studies did not specify which patients maintained subsequent therapy 70 , or did not examine session results unless patients actively requested it In one of these studies 70 , a possibly inadequate follow-up of subjects was mentioned, without giving them the opportunity to receive further treatment. One of the authors 72 suggested that short-term changes that occurred frequently in subjects' personality could be integrated and applied to their daily-life insight with greater support and additional help after hospital discharge.

In one study 65 , patients remained hospitalized at least one week after the LSD session, being visited by their therapists repeatedly. In another study 75 , a second dose was also offered to subjects in the active placebo group at months of follow-up open- label cross-over design.

Finally, in one of trials 70 , half of each group was also treated with disulfiram daily dose of mg after hospital discharge. Patients were strongly encouraged to take a fixed, prescribed dosage every day, instructed on the dangers of imbibing alcohol while on disulfiram, and started on the drug four days prior to hospital discharge.

They were given a six-month supply of disulfiram and instructed to take one mg tablet per day. Some studies 59 , 62 , 74 described efforts to predict therapeutic outcomes in relation to an acute hallucinogen experience. In one of them 59 , it was emphasized that the methodology used did not manage to measure crucial aspects of the experience that foresee subsequent benefits.

On the other hand, in two studies 59 , 74 it was observed that patients who seemed to benefit from the treatment with LSD did so optimally with more probability.

A greater likelihood of complete abstinence from alcohol 59 or optimal adjustment in the community 74 was observed after the LSD treatment. Despite design heterogeneity among the clinical trials in this review, some positive results were observed, revealing the therapeutic potential of LSD in the reduction of psychiatric symptomatology. The vast majority of authors described important positive short-term changes in patients, although in some studies 59 , 65 , 69 an important homogenization was observed between the LSD treatment group and the control group at long-term follow-up.

Some previous studies of lower quality 77 also exemplified a clear improvement in short-term adjustment, with a later tendency to balance results with the control group. However, this is in contrast with the results shown by some authors 62 , 74 , 75 , in which therapeutic changes were maintained at 6—12 months after treatment.

Moreover, in a follow-up study 78 beneficial changes were found at one year of follow-up for hallucinogen therapy compared with conventional psychotherapy in adolescent behavior disorders. Numerous studies in healthy volunteers have been carried out within the last decade, and some of them have showed positive effects more than a year after a LSD or psilocybin single dose 79 , The results of this review could conclude that alcohol use disorder patients may benefit from LSD treatment.

Other studies with a lower quality control group patients did not receive a treatment comparable to the treatment group also found significant differences in favor of LSD treatment in alcoholism 60 , Likewise, according to a retrospective analysis of studies published in the late s, LSD is a potential therapeutic agent for the treatment of chronic alcoholism A recent meta-analysis 83 of six of the clinical trials chosen for this review showed the superiority of LSD over placebo in the treatment of alcoholism with an odds ratio OR of 1.

This study found that a LSD single dose was comparable in terms of effectiveness with the daily intake of naltrexone, acamprosate, or disulfiram in alcoholism treatment 84 — Other studies in our review also found promising results regarding LSD use for the treatment of heroin use disorder, anxiety, depression, psychosomatic illnesses, and anxiety in relation to life-threatening diseases.

Regarding the latter, several authors 56 , 57 emphasize the difficulty of designing placebo-controlled and double-blind trials, due to ethical reasons and the nature of the psychoactive intervention. Regarding the disparity between some results in our review, and as noted by Pahnke et al.

LSD invariably involves a complex interaction between drug dosage, set and setting. This link is also objectified in different studies, showing the significant relationship between the therapeutic efficacy of hallucinogens and an adequate set, setting and integration of later experience 62 , 87 — Some authors 91 argued that the accepted methods proven to generate some beneficial experience with LSD are far from those used by Smart at the s.

Therefore, the inherent difficulty in conducting a double blind controlled clinical trials with LSD should be mentioned. In , Whitaker 92 stated his opposition to the design of a control group with this type of substance, due to the promising responses of first patients as opposed to the control group. Also, modern clinical trials are currently facing a series of problems, which could be summarized as follows Firstly, subjective and objective changes experienced with LSD and the rest of hallucinogens, apparent for both the subject and observer, make performing double-blind tests virtually impossible.

Likewise, adequate placebo control becomes extremely difficult due to the absence of such changes in the control group. Strict control of the variables related to the therapeutic benefits of LSD is also necessary. Finally, research with these substances must overcome a series of strict ethical committees and restrictions at the legal level. When attempting to solve difficulties in terms of blinding and adequate placebo control, a valid approach is an active placebo, using LSD at lower doses 94 , an approach already suggested within some of clinical trials in our review 62 , This methodology, despite possibly minimizing the effects of LSD when compared to its sole administration, is based on results by numerous researchers who have observed the link between dose and quality and intensity of the hallucinogen response 95 — Dosage and form of administration, as well as the context in which it is carried out, can be strictly controlled within a hospital setting.

The possible effects of microdoses of LSD must be takin into account, possibly limiting its use. Despite the known unpredictability of hallucinogens, great efforts have been made in recent years to know which variables are associated with the therapeutic value of these substances, finding mystical-type experiences as one of the objectives to be achieved 97 , 99 , Results of recent investigations show that mystical-type experiences are associated with positive long-term changes after a dose of hallucinogens 33 , 79 , 99 — The musical stimuli variable has also been observed as a predictor of mystical-type experiences and positive therapy outcomes As noted by Gasser 76 , designing qualitative studies, not only based on pathology-oriented measurements, is also important to detect variables related to other psychopathological symptoms that can potentially be improved by LSD use e.

The apparently unpredictable nature of these experiences makes studying them in empirical research equally difficult and necessary 14 , , Moreover, numerous recent studies with LSD regarding changes in neural networks have been carried out.

Modularity and integration networks as observed in resting- state functional connectivity have been shown to decrease due to effects of LSD , Likewise, multiple modern clinical trials involving other hallucinogens have been carried out in the last decade, mainly with psilocybin. Hopeful results have been found for the treatment of alcohol or tobacco addiction, anxiety in relation to advanced cancer or obsessive-compulsive disorder Some possible reasons for the greater use of psilocybin over LSD in modern trials were the shorter duration of one effects of the former thus avoiding hospitalization or the greater stigma that prevailed regarding the latter making it difficult to get economic funds and the approval by ethical committees.

Beyond psychiatry, the therapeutic potential of LSD in other medicine fields has recently become evident, as in the treatment of cluster headaches in neurology As it has been previously pointed out, the homogenization of the therapeutic approach is strictly necessary, and training programs related to research and psychotherapy with hallucinogens have recently been developed Also, there are modern guidelines available for the correct use of hallucinogens in clinical research Therefore, the reborn interest of the therapeutic potential of hallucinogens in modern clinical trials is evident, something proven by the remarkable increase in the number of studies carried out with these substances over the last decade The present review has limitations.

Firstly, only articles written in English were selected; this could imply that articles in other languages were excluded despite the fact that these might have provided valuable information. Furthermore, as mentioned above, most studies were carried out during the past century. Moreover and as previously discussed, there was considerable heterogeneity in their design. Also, differences regarding patient populations, features, and diagnostic methods were noticed. Therefore, due to the lack of studies and the features exhibited by selected research, this review can contribute limited evidence on the topic of interest.

This study comes with its own set of strengths. On the one hand, to our knowledge this is the first systematic review of randomized-controlled trials to assess the therapeutic potential of LSD in psychiatry. On the other, a strict selection of studies was carried out, considering inclusion and exclusion criteria as well as confounding factors.

With regards to this and in spite of the heterogeneity mentioned above, the important therapeutic value of LSD is revealed and it is observed to be related to variables controlled by the researcher, such as: set, setting and aftercare related to the LSD session.

Another positive aspect of this review is that our results highlight the need for randomized-controlled clinical trials with standardized methods to accurately assess the quality of an acute hallucinogen experience.

Finally, this review could serve as a guide for further research involving LSD as a therapeutic agent. In conclusion, and despite some controversial results mentioned above, LSD is revealed as a potential therapeutic agent in psychiatry; the evidence to date is strongest for the use of LSD in the treatment of alcoholism. Despite the difficulty of designing double-blind clinical trials with this substance, new studies performed under modern standards are necessary in order to strengthen our knowledge, help erase the stigma that still prevails around these substances and open new doors in the future.

JF and FF reviewed the abstracts and the papers. JF and ME obtained the data from the selected articles. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

National Center for Biotechnology Information , U. Journal List Front Psychiatry v. Front Psychiatry. Published online Jan Author information Article notes Copyright and License information Disclaimer. This article was submitted to Psychopharmacology, a section of the journal Frontiers in Psychiatry. Received Aug 28; Accepted Nov The use, distribution or reproduction in other forums is permitted, provided the original author s and the copyright owner s are credited and that the original publication in this journal is cited, in accordance with accepted academic practice.

No use, distribution or reproduction is permitted which does not comply with these terms. This article has been cited by other articles in PMC. Abstract Lysergic acid diethylamide LSD was studied from the s to the s to evaluate behavioral and personality changes, as well as remission of psychiatric symptoms in various disorders.

Keywords: lysergic acid diethylamide LSD , hallucinogens, therapeutic use, psychiatric disorders, addiction. Introduction Since its discovery in by Swiss chemist Albert Hofmann 1 , lysergic acid diethylamide lysergide, LSD has maintained an unstable relationship with psychiatry. Data Items Dosage, frequency and duration of the treatment, for both experimental and control interventions were extracted. Eligibility Criteria Randomized controlled trials of LSD as a therapeutic tool for psychiatry were included.

Quality Assessment The Cochrane Collaboration risk of bias assessment tool was used to determine the quality of the studies Results A total of 3, papers were identified through the search in Pubmed, and 12 additional records were found through other sources manual search based on review papers and meta-analysis. Open in a separate window. Figure 1. You could be eligible to participate in a psychedelic clinical trial for research.

Psychedelic studies in various stages, enroll both healthy volunteers and individuals with specific mental health conditions. Below is an up-to-date and searchable compilation of psychedelic clinical trials registered on clinicaltrials. When you find a study location in your area for a condition you have, contact the study sites through the listings in the clinical trial records provided below.

Browse our clinical trials database and filter by substance, location, condition, and enrollment status. Studies are displayed on a map and list. Research around the world is expanding quickly. New investigations for the therapeutic use of psychedelics , as well as inquiries into how the brain and consciousness works, are appearing all the time. The forerunners in this field pave the way for others by contributing evidence-based findings to the body of knowledge.

Several organizations, academic institutions, and corporations are leading the psychedelic clinical trial and research field forward. The Heffter Research Institute and the Beckley Foundation are pioneering non-profit organizations funding and supporting many dimensions of psychedelic research. The Usona Institute conducts pre-clinical and clinical research to further the understanding of the therapeutic effects of psilocybin and other consciousness-expanding medicines.

The Multidisciplinary Association for Psychedelic Studies MAPS is non-profit research and educational organization that develops medical, legal, and cultural contexts for people to benefit from the careful uses of psychedelics and marijuana. With regard to potential therapeutic long-term effects of single-dose hallucinogen administration, unclear is whether these effects depend on a direct pharmacological action or on the acute psychological response.

Differential indications might be associated with different aspects of mechanisms of action. Novel dose—response studies of the acute effects of LSD are lacking, and direct comparisons with psilocybin need to be made. Neuroimaging studies may help determine whether long-term changes in mood can be linked to changes in brain activity and how such patterns change before, during, and after the acute effects of LSD and other hallucinogens.

The dissociable effects of the substance itself and psychotherapy on outcomes also need to be elucidated, in addition to their interactive effects. Larger studies need to validly define the benefits of using hallucinogens as an adjunct to psychotherapy and the patient characteristics that may predict such additional benefits of hallucinogens.

Unclear are the aspects of the acute response to hallucinogens that best predict good long-term therapeutic outcomes. Acute mystical-type effects of psilocybin have been associated with greater reductions of anxiety and depression in patients Garcia-Romeu et al , ; Griffiths et al , ; Ross et al , This association, however, may not imply causation.

Other aspects of the acute peak response to hallucinogens could be equally important Dolder et al , ; Liechti et al , Many practical aspects of clinical trials that evaluate the effects of LSD also need to be resolved. Clinical studies have generally become extremely costly because of overregulation. This is especially problematic for LSD research because industry funding is unlikely. In many countries, the scheduling of LSD still impedes or prohibits clinical research.

The mechanism of the therapeutic actions of LSD is unclear. Enhanced neurogenesis may be associated with antidepressant effects. Acutely reduced fear recognition and amygdala reactivity may facilitate the processing of negative information Dolder et al , ; Mueller et al , a , and feelings of closeness and trust enhance the patient—therapist relationship Dolder et al , ; Schmid et al , Irrespective of the mechanism, if LSD in only a few doses may indeed improve health, this novel treatment paradigm needs to be studied further in modern clinical studies.

A few single administrations of LSD or related substances within a therapeutic setting may be beneficial for patients with anxiety associated with severe illness, depression, or addiction.

These old—new treatments may have a potential in psychiatry. As professionals, we should actively study these new options so patients who are in need will not look elsewhere for unproven treatments from unregulated sources. More methodologically sound research on the psychological and biological mechanisms and therapeutic potential of LSD in psychiatry is needed.

National Center for Biotechnology Information , U. Journal List Neuropsychopharmacology v. Published online Jun Prepublished online Apr Author information Article notes Copyright and License information Disclaimer. This article has been cited by other articles in PMC. Abstract All modern clinical studies using the classic hallucinogen lysergic acid diethylamide LSD in healthy subjects or patients in the last 25 years are reviewed herein.

Introduction The present article reviews studies on the clinical pharmacology and use of lysergic acid diethylamide LSD in psychiatry research, with a focus on recent clinical studies. History LSD was first synthesized in , and its psychoactive properties were discovered in Receptor interaction profile and mechanism of action Serotonergic hallucinogens can be classified based on their chemical structure as phenethylamines and tryptamines.

Open in a separate window. Studies in healthy subjects Five novel experimental placebo-controlled studies have been conducted in Basel, London, and Zurich in a total of 95 normal subjects Table 2.

Subjective Effects Modern placebo-controlled studies using validated psychometric scales have only recently been conducted Carhart-Harris et al , b ; Kraehenmann et al , ; Preller et al , ; Schmid et al , Figure 1. Autonomic and Adverse Effects LSD moderately increased blood pressure, heart rate, body temperature, and pupil size Dolder et al , ; Kaelen et al , ; Schmid et al , Endocrine Effects LSD acutely increased plasma concentrations of cortisol Strajhar et al , , prolactin, oxytocin, and epinephrine Schmid et al , Emotional Processing LSD impaired the recognition of sad and fearful faces Dolder et al , and enhanced emotional empathy Dolder et al , , similar to psilocybin Kometer et al , ; Preller et al , and MDMA Hysek et al , a ; Kuypers et al , Functional Brain Imaging LSD acutely decreased the functional integrity of brain networks Figure 2a and the separation between networks Carhart-Harris et al , c ; Tagliazucchi et al , Figure 2b.

Figure 2. Figure 3. Figure 4. Mid- and Long-Term Effects In comparison to other illicit substances, epidemiological studies indicate that the use of classic hallucinogens is associated with lower psychological distress, lower suicidality, and lower mental health problems Hendricks et al , Studies in patients Early studies from the s to s indicated that LSD may have antidepressive and anxiolytic properties Dos Santos et al , ; Passie et al , ; Rucker et al , Future directions New areas of research on hallucinogens, including LSD, have just recently opened, and many questions remain unanswered.

Conclusions A few single administrations of LSD or related substances within a therapeutic setting may be beneficial for patients with anxiety associated with severe illness, depression, or addiction. Funding and disclosure The authors declare no conflict of interest.

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