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Lysergic acid diethylamide LSD is a potent hallucinogenic substance that was extensively investigated by psychiatrists during the s and s. Researchers were interested in the unique effects induced by this substance, some of which resemble symptoms seen in schizophrenia.

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Effects of lsd use

View all 11 Articles. 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.

LSD was used in the treatment of anxiety, depression, psychosomatic diseases and addiction. However, most of the studies were not performed under contemporary standards, and it has taken several decades for a resurgence of interest in LSD research and its therapeutic potential for psychiatry.

The aim of this review is to identify controlled and randomized clinical trials that assess the potential use of LSD in psychiatry.

A literature search of PubMed and Psychedelic bibliography from Multidisciplinary Association for Psychedelic Studies MAPS databases was performed as well as a manual search of references from evaluated studies. Only randomized-controlled clinical trials were included.

Study quality was systematically calculated by using the Cochrane Collaboration Tool for assessing risk of bias.

Harmful effects of lsd

A final selection of 11 articles was made after considering inclusion and exclusion criteria. LSD was administered to patients in a dose ranging from 20 to mcg. Despite the de heterogeneity of clinical trials, positive were observed, thus revealing the therapeutic potential of LSD to reduce psychiatric symptomatology, mainly in alcoholism. The vast majority of authors describe ificant and positive short-term changes in patients, despite the fact that in some studies an important homogenization was observed between the LSD treatment group and control group at long-term follow-up.

What is lsd?

Multiple variables regarding LSD treatment therapeutic approach and quality of experience were revealed and related to therapeutic outcomes. 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 deing proper double blind clinical trials with this substance, new studies that conform to modern standards are necessary in order to strengthen our knowledge on its use and open new doors in the future.

Since its discovery in by Swiss chemist Albert Hofmann 1lysergic acid diethylamide lysergide, LSD has maintained an unstable relationship with psychiatry. Hofmann synthesized LSD in an effort to develop ergot derivatives with the goal of reducing postpartum hemorrhage.

Some years later, after accidentally getting into contact with a small dose, he was the first subject in history to Medical effects of lsd its effects 2. After its prohibition in USA indue to an increase in popularity and its association with counter-cultural movements, it has taken several decades for a resurgence of interest in its therapeutic potential for psychiatry 6 — 9. Classical hallucinogens are psychoactive substances that are believed to mediate their effects mainly through an agonist activity in the serotonin 2A receptor 5-HT2A Experimental studies have ly shown that the use of 5-HT2A antagonists attenuate the main effects of these substances, both in rats 1718 and human subjects 19 — Other receptors which may contribute to the effects of these agents are the serotonin 2C and 1A receptors, as well as other effects in the dopaminergic and noradrenergic system Likewise, these are potent regulators of transcription factors, which could mediate a potential mechanism of action in the synaptic structure with greater persistence of their effects over time 23 LSD is one of the most potent classical hallucinogens available, with active doses between 0.

Its half-life is approximately 3 h, varying between 2 and 5 h, and its psychoactive effects are prolonged over time up to 12 h depending on the dose, tolerance, weight and age of the subject 25 Recently LSD has been used in microdoses as low as 10 mcg to enhance performance The usual mental effects of LSD are distortion of sense of time and identity, alteration in depth and time perception, visual hallucinations, sense of euphoria or certainty, distorted perception of the size and shape of objects, movements, color, sounds, touch and body image and delusions Concerning safety, the administration of classical hallucinogens carries some risks.

Another possible risk is the exacerbation of psychotic disorders or the generation of prolonged psychotic reactions, which could be related to the subject's predisposition Although no contemporary study has reported psychosis after the administration of classical hallucinogens, an adequate screening of psychotic episodes and the patient's vulnerability is necessary for the use of these substances Another possible adverse effect is a modest increase in blood pressure and heart rate; therefore, patients with severe cardiovascular disease should be excluded from the administration of this agent.

Other usual absolute contraindications are pregnancy, epilepsy or paranoid personality traits The remaining adverse effects should not limit its therapeutic use 31 As a recreational drug, LSD does not entail physical dependence as withdrawal syndrome, as do most of these substances opioids, cocaine, cannabis and methamphetamine Its frequent or long-term use can lead to tolerance, and after a single dose, emotional, physical and mental stability is quickly recovered 35 Likewise, classical hallucinogens in general, and LSD in particular, exhibit very low physiological toxicity, even at very high doses, without any evidence of organic damage or neuropsychological deficits 3637 associated with their use.

Medical effects of lsd safety has recently led to considering LSD as one of the safest psychoactive recreational substances 38 — However, LSD remains one of the most stigmatized and legally restricted agents among psychoactive substances.

Systematic review article

It is still included in Schedule I of the United Nations classification of drugs, restricting its use in research and making it difficult to potentially use it as a therapeutic tool in medicine. This classification has recently been questioned by various authors 8 A few decades ago, anecdotal reports of suicidal acts in recreational users were published, and intensely emphasized by the Medical effects of lsd 44 These attempts are in contrast with some recent population studies, which show ificant associations between the use of a single dose of classical hallucinogens and a decrease in the likelihood of psychological distress and suicide 46 — Other recent studies also established a clear link between life-time use of classical hallucinogens and a lower probability of developing mental problems, as well as a positive association, although non-ificant, regarding several variables related to mental health 49 Nevertheless, the unpredictability of subject behavior makes it necessary to adequately control the environment and monitor the reaction of each individual.

Regarding its therapeutic potential, LSD was used from the s to the s to achieve behavioral and personality changes, as well as remission of psychiatric symptoms in various disorders 30 LSD was used in the treatment of anxiety, depression, psychosomatic diseases and addiction During that time, it was also observed that LSD together with suitable accompaniment during its administration, could reduce pain, anxiety and depression in patients with advanced cancer 53 — 55 Other studies involving larger patient samples also established its safety and promising in patients with terminal cancer 56 Studies in schizophrenic patients, however, reached less response to the same dose 58 and worse clinical outcomes 59 compared with non-schizophrenics patients, and negative effects on these patients have been described, both in LSD experience itself and later benefits 60 The data indicate that the responsivity of schizophrenic patients to the administration of lysergic acid is less than that of normal subjects.

Prediction of individual responses to LSD depends on several variables, some of which were already discussed at the international LSD therapy conference in In psycholytic therapy, mainly practiced in Europe, low-moderate doses mcg of this drug were used in more than one therapeutic session of psychodynamic orientation. In psychedelic-chemotherapy, Medical effects of lsd use itself was emphasized at relatively high doses mcg or morewith a very limited or absent psychotherapeutic approach.

This approach should include the proper prior preparation of the patient set and a comfortable environment during the session settingas well as a discussion on it during subsequent follow-up sessions with the subject after-care related to LSD session Mystical experiences are referred to as those in which a sense of unity with the environment is experienced achieving a vivid transcendental experience at an emotional, cognitive and ego-structural level, after a and personal therapeutic preparation The aim is to catalyze rapid and fundamental changes in the value system and self-image of the subject Despite the foregoing, most clinical studies involving the use of LSD were published between the s and s, up to the strict prohibition of its use in research.

Lsd's effects on your brain

Obviously, most of these studies were not performed under contemporary standards. The purpose of this systematic review is to identify controlled and randomized clinical trials that assess the potential use of LSD in psychiatry and identify variables controlled by the researcher as potentially related to therapeutic outcomes. This is with the aim of informing a discussion on the benefits and challenges of integrating contemporary classic hallucinogens research into modern clinical trial des and providing a guide for further research involving LSD as a therapeutic agent.

To ensure literature saturation, the electronic search was supplemented by a manual review of the reference lists from eligible publications.

Two authors independently screened the titles and abstracts yielded by the search against the inclusion criteria. Full reports for all titles that appear to meet the inclusion criteria were obtained. Reviewers resolved disagreements by discussion. The search was limited to the time period compressed between andbased on the obtained in the reference search.

Lsd as a treatment

Each potentially relevant publication found during the search was retrieved and assessed for its use in this review after inclusion and exclusion criteria were specified. 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.

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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.

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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.

Introduction

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.

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