OPEN Foundation

D. Newcombe

Methylenedioxymethamphetamine (MDMA) in Psychiatry: Pros, Cons, and Suggestions.

Abstract

BACKGROUND:
For a number of mental health disorders, including posttraumatic stress disorders (PTSD), there are not many available treatment options. Recently, there has been renewed interest in the potential of methylenedioxymethamphetamine (MDMA) to restore function for patients with these disorders. The primary hypothesis is that MDMA, via prosocial effects, increases the ability of patients to address the underlying psychopathology of the disorder. However, the use of MDMA poses potential problems of neurotoxicity, in addition to its own potential for misuse.
METHODS:
In this article, the proposed potential of MDMA as an adjunct to psychotherapy for PTSD is evaluated. The rationale for the use of MDMA and the positive results of studies that have administered MDMA in the treatment of PTSD are provided (pros). A description of potential adverse effects of treatment is also presented (cons). An overview of MDMA pharmacology and pharmacokinetics and a description of potential adverse effects of treatments are also presented. Methylenedioxymethamphetamine-produced oxytocin release and decreased expression of fear conditioning as well as one of the MDMA enantiomers (the n R- entaniomer) are suggested as potential mechanisms for the beneficial effects of MDMA in PTSD (suggestions).
RESULTS:
There is some evidence that MDMA facilitates recovery of PTSD. However, the significant adverse effects of MDMA raise concern for its adoption as a pharmacotherapy. Alternative potential treatments with less adverse effects and that are based on the ubiquitous pharmacology of MDMA are presented.
CONCLUSIONS:
We suggest that additional research investigating the basis for the putative beneficial effects of MDMA might reveal an effective treatment with fewer adverse effects. Suggestions of alternative treatments based on the behavioral pharmacology and toxicology of MDMA and its enantiomers are presented.
Schenk, S., & Newcombe, D. (2018). Methylenedioxymethamphetamine (MDMA) in Psychiatry: Pros, Cons, and Suggestions. Journal of clinical psychopharmacology38(6), 632-638., 10.1097/JCP.0000000000000962
Link to full text

Methylenedioxymethamphetamine (MDMA) in Psychiatry: Pros, Cons, and Suggestions.

Abstract

BACKGROUND:
For a number of mental health disorders, including posttraumatic stress disorders (PTSD), there are not many available treatment options. Recently, there has been renewed interest in the potential of methylenedioxymethamphetamine (MDMA) to restore function for patients with these disorders. The primary hypothesis is that MDMA, via prosocial effects, increases the ability of patients to address the underlying psychopathology of the disorder. However, the use of MDMA poses potential problems of neurotoxicity, in addition to its own potential for misuse.
METHODS:
In this article, the proposed potential of MDMA as an adjunct to psychotherapy for PTSD is evaluated. The rationale for the use of MDMA and the positive results of studies that have administered MDMA in the treatment of PTSD are provided (pros). A description of potential adverse effects of treatment is also presented (cons). An overview of MDMA pharmacology and pharmacokinetics and a description of potential adverse effects of treatments are also presented. Methylenedioxymethamphetamine-produced oxytocin release and decreased expression of fear conditioning as well as one of the MDMA enantiomers (the n R- entaniomer) are suggested as potential mechanisms for the beneficial effects of MDMA in PTSD (suggestions).
RESULTS:
There is some evidence that MDMA facilitates recovery of PTSD. However, the significant adverse effects of MDMA raise concern for its adoption as a pharmacotherapy. Alternative potential treatments with less adverse effects and that are based on the ubiquitous pharmacology of MDMA are presented.
CONCLUSIONS:
We suggest that additional research investigating the basis for the putative beneficial effects of MDMA might reveal an effective treatment with fewer adverse effects. Suggestions of alternative treatments based on the behavioral pharmacology and toxicology of MDMA and its enantiomers are presented.
Schenk, S., & Newcombe, D. (2018). Methylenedioxymethamphetamine (MDMA) in Psychiatry: Pros, Cons, and Suggestions. Journal of clinical psychopharmacology38(6), 632-638., 10.1097/JCP.0000000000000962
Link to full text

Ibogaine for treating drug dependence. What is a safe dose?

Abstract

The indole alkaloid ibogaine, present in the root bark of the West African rain forest shrub Tabernanthe iboga, has been adopted in the West as a treatment for drug dependence. Treatment of patients requires large doses of the alkaloid to cause hallucinations, an alleged integral part of the patient’s treatment regime. However, case reports and case series continue to describe evidences of ataxia, gastrointestinal distress, ventricular arrhythmias and sudden and unexplained deaths of patients undergoing treatment for drug dependence. High doses of ibogaine act on several classes of neurological receptors and transporters to achieve pharmacological responses associated with drug aversion; limited toxicology research suggests that intraperitoneal doses used to successfully treat rodents, for example, have also been shown to cause neuronal injury (purkinje cells) in the rat cerebellum. Limited research suggests lethality in rodents by the oral route can be achieved at approximately 263mg/kg body weight. To consider an appropriate and safe initial dose for humans, necessary safety factors need to be applied to the animal data; these would include factors such as intra- and inter-species variability and for susceptible people in a population (such as drug users). A calculated initial dose to treat patients could be approximated at 0.87mg/kg body weight, substantially lower than those presently being administered to treat drug users. Morbidities and mortalities will continue to occur unless practitioners reconsider doses being administered to their susceptible patients.
Schep, L. J., Slaughter, R. J., Galea, S., & Newcombe, D. (2016). Ibogaine for treating drug dependence. What is a safe dose?. Drug and alcohol dependence166, 1-5. 10.1016/j.drugalcdep.2016.07.005
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