Hallucinogens and Their Therapeutic Use: A Literature Review

Begola, Matthew J; Schillerstrom, Jason E.

doi:10.1097/pra.0000000000000409

Cited by 11 publications

(6 citation statements)

References 29 publications

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“…Humans have used psychedelics (also known as serotonergic hallucinogens) for thousands of years. Nonetheless, scientists became interested in these substances only after Albert Hofmann discovered the psychoactive properties of lysergic acid diethylamide (LSD) in 1943 (Begola and Schillerstrom 2019). Although hallucinogens are derived from multiple structural families, they are known as powerful agents producing profound changes in consciousness, perception, and mood (Halberstadt 2015).…”

Section: Introductionmentioning

confidence: 99%

Tolerance to neurochemical and behavioral effects of the hallucinogen 25I-NBOMe

et al. 2021

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Rationale 4-Iodo-2,5-dimethoxy-N-(2-methoxybenzyl)phenethylamine (25I-NBOMe) is a potent serotonin 5-HT2A/2C receptor agonist with hallucinogenic activity. There is no data on the 25I-NBOMe effect on brain neurotransmission and animal performance after chronic administration. Objectives We examined the effect of a 7-day treatment with 25I-NBOMe (0.3 mg/kg/day) on neurotransmitters’ release and rats’ behavior in comparison to acute dose. Methods Changes in dopamine (DA), serotonin (5-HT), acetylcholine (ACh), and glutamate release were studied using microdialysis in freely moving rats. The hallucinogenic activity was measured in the wet dog shake (WDS) test. The animal locomotion was examined in the open field (OF) test, short-term memory in the novel object recognition (NOR) test. The anxiogenic/anxiolytic properties of the drug were tested using the light/dark box (LDB) test. Results Repeated administration of 25I-NBOMe decreased the response to a challenge dose of DA, 5-HT, and glutamatergic neurons in the frontal cortex as well as weakened the hallucinogenic activity in comparison to acute dose. In contrast, striatal and accumbal DA and 5-HT release and accumbal but not striatal glutamate release in response to the challenge dose of 25I-NBOMe was increased in comparison to acute treatment. The ACh release was increased in all brain regions. Behavioral tests showed a motor activity reduction and memory deficiency in comparison to a single dose and induction of anxiety after the drug’s chronic and acute administration. Conclusions Our findings suggest that multiple injections of 25I-NBOMe induce tolerance to hallucinogenic activity and produce alterations in neurotransmission. 25I-NBOMe effect on short-term memory, locomotor function, and anxiety seems to be the result of complex interactions between neurotransmitter pathways.

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Section: Introductionmentioning

confidence: 99%

Tolerance to neurochemical and behavioral effects of the hallucinogen 25I-NBOMe

et al. 2021

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“…It is suggested that naturally-occurring psychedelics have therapeutic potential due to the formation of new neural connections and modulation of the monoamine neurotransmitter system ( Carhart-Harris et al, 2018 ; Erritzoe et al, 2018 ). Recent evidence suggests that psychedelics can benefit various clinical populations, with rapid and sustained advances in post-treatment outcomes documented for depression ( Griffths and Grob, 2010 ; Begola and Schillerstrom, 2019 ), anxiety ( Griffths and Grob, 2010 ), and addictions ( Bogenschutz et al, 2015 ; Bogenschutz and Johnson, 2016 ). Importantly, the current evidence verified in animal studies has shown that classical psychedelics are not associated with physical dependence, abuse or withdrawal and have a low level of toxicity ( Reiff et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Three Naturally-Occurring Psychedelics and Their Significance in the Treatment of Mental Health Disorders

Vorobyeva¹,

Kozlova

2022

Front. Pharmacol.

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Classical psychedelics represent a family of psychoactive substances with structural similarities to serotonin and affinity for serotonin receptors. A growing number of studies have found that psychedelics can be effective in treating various psychiatric conditions, including post-traumatic stress disorder, major depressive disorder, anxiety, and substance use disorders. Mental health disorders are extremely prevalent in the general population constituting a major problem for the public health. There are a wide variety of interventions for mental health disorders, including pharmacological therapies and psychotherapies, however, treatment resistance still remains a particular challenge in this field, and relapse rates are also quite high. In recent years, psychedelics have become one of the promising new tools for the treatment of mental health disorders. In this review, we will discuss the three classic serotonergic naturally occurring psychedelics, psilocybin, ibogaine, and N, N-dimethyltryptamine, focusing on their pharmacological properties and clinical potential. The purpose of this article is to provide a focused review of the most relevant research into the therapeutic potential of these substances and their possible integration as alternative or adjuvant options to existing pharmacological and psychological therapies.

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“…Consequently, there has been a shift within psychiatry to identify novel agents that can withstand scientific scrutiny (Begola & Schillerstrom, 2019 ; Stein & Simon, 2021 ). This shift has been associated with a re-examination of psychedelic agents for PTSD, including 3,4-methylenedioxymethamphetamine (MDMA/‘ecstasy’), psilocybin (‘magic mushrooms’), and ketamine (‘Special-K’; Varker et al, 2021 ).…”

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confidence: 99%

So how special is special K? A systematic review and meta-analysis of ketamine for PTSD RCTs

Borgogna,

Owen,

Vaughn

et al. 2024

European Journal of Psychotraumatology

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Background: PTSD is a significant mental health problem worldwide. Current evidence-based interventions suffer various limitations. Ketamine is a novel agent that is hoped to be incrementally better than extant interventions. Objective: Several randomized control trials (RCTs) of ketamine interventions for PTSD have now been published. We sought to systematically review and meta-analyse results from these trials to evaluate preliminary evidence for ketamine’s incremental benefit above-and-beyond control interventions in PTSD treatment. Results: Omnibus findings from 52 effect sizes extracted across six studies ( n = 221) yielded a small advantage for ketamine over control conditions at reducing PTSD symptoms ( g = 0.27, 95% CI = 0.03, 0.51). However, bias-correction estimates attenuated this effect (adjusted g = 0.20, 95%, CI = −0.08, 0.48). Bias estimates indicated smaller studies reported larger effect sizes favouring ketamine. The only consistent timepoint assessed across RCTs was 24-hours post-initial infusion. Effects at 24-hours post-initial infusion suggest ketamine has a small relative advantage over controls ( g = 0.35, 95% CI = 0.06, 0.64). Post-hoc analyses at 24-hours post-initial infusion indicated that ketamine was significantly better than passive controls ( g = 0.44, 95% CI = 0.03, 0.85), but not active controls ( g = 0.24, 95% CI = −0.30, 0.78). Comparisons one-week into intervention suggested no meaningful group differences ( g = 0.24, 95% CI = 0.00, 0.48). No significant differences were evident for RCTs that examined effects two-weeks post initial infusion ( g = 0.17, 95% CI = −0.10, 0.44). Conclusions: Altogether, ketamine-for-PTSD RCTs reveal a nominal initial therapeutic advantage relative to controls. However, bias and heterogeneity appear problematic. While rapid acting effects were observed, all control agents (including saline) also evidenced rapid acting effects. We argue blind penetration to be a serious concern, and that placebo is the likely mechanism behind reported therapeutic effects.

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Hallucinogens and Their Therapeutic Use: A Literature Review

Cited by 11 publications

References 29 publications

Tolerance to neurochemical and behavioral effects of the hallucinogen 25I-NBOMe

Tolerance to neurochemical and behavioral effects of the hallucinogen 25I-NBOMe

Three Naturally-Occurring Psychedelics and Their Significance in the Treatment of Mental Health Disorders

So how special is special K? A systematic review and meta-analysis of ketamine for PTSD RCTs

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