Dose for mdma
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Optimal Dose for MDMA in Therapeutic and Recreational Contexts
Introduction to MDMA Dosage
3,4-Methylenedioxymethamphetamine (MDMA), commonly known as ecstasy, is a psychoactive drug that has been studied for both its therapeutic potential and its recreational use. Understanding the optimal dosage is crucial for maximizing benefits while minimizing risks.
Therapeutic Use of MDMA: PTSD Treatment
MDMA-Assisted Psychotherapy for PTSD
MDMA has shown promise in treating post-traumatic stress disorder (PTSD), particularly in military veterans, firefighters, and police officers. A phase 2 clinical trial assessed the efficacy and safety of MDMA-assisted psychotherapy with doses of 30 mg, 75 mg, and 125 mg1. The study found that both 75 mg and 125 mg doses significantly reduced PTSD symptoms compared to the 30 mg dose, with the 75 mg dose showing the most substantial effect size1.
Safety and Efficacy
The trial reported that MDMA was well-tolerated, with no serious adverse events directly related to the drug1. Another study corroborated these findings, indicating that MDMA can be safely administered in a clinical setting without significant adverse effects5.
Recreational Use: Safety and Pharmacokinetics
Acute Effects and Safety Profile
In recreational settings, MDMA is often consumed in doses ranging from 75 mg to 125 mg. A study on healthy subjects revealed that a 125 mg dose produced more pronounced positive effects but also increased adverse effects such as hypertension, tachycardia, and hyperthermia compared to a 75 mg dose2. These effects were more significant in women, suggesting a need for gender-specific dosage considerations2.
Repeated Doses and Metabolic Inhibition
MDMA exhibits non-linear pharmacokinetics, meaning that its effects and plasma concentrations do not increase proportionally with higher doses. This non-linearity is due to metabolic inhibition, particularly involving the cytochrome P450 2D6 enzyme3 9. Studies have shown that repeated doses, even when taken 4 hours apart, can lead to a disproportionate increase in plasma MDMA levels, heightening the risk of acute toxicity7 10.
Conclusion
The optimal dose of MDMA varies depending on the context of use. For therapeutic purposes, doses of 75 mg and 125 mg have been effective in reducing PTSD symptoms, with the 75 mg dose showing the most significant benefits and fewer adverse effects1 5. In recreational settings, while doses of 75 mg to 125 mg are common, the higher end of this range increases the risk of adverse cardiovascular and thermoregulatory effects, particularly in women2. Understanding these nuances is essential for maximizing the therapeutic benefits of MDMA while minimizing its risks in both clinical and recreational contexts.
Sources and full results
Most relevant research papers on this topic
3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers: a randomised, double-blind, dose-response, phase 2 clinical trial.
MDMA-assisted psychotherapy is effective and safe for treating chronic PTSD in military veterans, firefighters, and police officers.
RCT
Very Rigorous Journal
Highly CitedSafety pharmacology of acute MDMA administration in healthy subjects
MDMA administration is generally safe in healthy subjects, but risks are likely higher in patients with cardiovascular disease and psychiatric disorders.
RCTVery Rigorous JournalHighly CitedRepeated doses administration of MDMA in humans: pharmacological effects and pharmacokinetics
Repeated doses of MDMA (24 hours apart) result in higher pharmacological effects but lower metabolic inhibition, with effects similar to those observed after the first dose.
RCT
Rigorous JournalHighly CitedA QTL on rat chromosome 7 modulates prepulse inhibition, a neuro-behavioral trait of ADHD, in a Lewis x SHR intercross
Chronic exposure to MDMA in rats leads to behavioral sensitization, but does not cross-sensitize with other psychostimulants like amphetamine and methylphenidate.
Non-RCT
Animal StudyHighly CitedA randomized, controlled pilot study of MDMA (±3,4-Methylenedioxymethamphetamine)-assisted psychotherapy for treatment of resistant, chronic Post-Traumatic Stress Disorder (PTSD)
MDMA-assisted psychotherapy is safe and effective for treating treatment-resistant PTSD, with three sessions being more effective than two.
RCTVery Rigorous JournalHighly CitedCardiovascular and neuroendocrine effects and pharmacokinetics of 3, 4-methylenedioxymethamphetamine in humans.
MDMA significantly increases blood pressure, heart rate, and pupillary diameter, potentially causing toxicity in real-life conditions.
RCTHighly CitedHuman pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) after repeated doses taken 4h apart Human pharmacology of MDMA after repeated doses taken 4h apart
Repeated doses of MDMA, separated by 4 hours, result in acute tolerance to its effects, with most effects similar to single doses except for systolic blood pressure and reaction time.
RCTPlasma, oral fluid and sweat wipe ecstasy concentrations in controlled and real life conditions.
Oral fluid concentrations of MDMA can exceed plasma concentrations, with a peak of 1215 ng/ml observed in a controlled study, and multiple drug use conditions revealing higher concentrations in oral fluid samples.
RCTHighly CitedSelf-injection of d,1-3,4-methylenedioxymethamphetamine (MDMA) in the baboon
MDMA self-injection in baboons leads to more injections and higher responses rates than saline, but its maximal response rate is less than that maintained with cocaine, and its cyclic pattern can suppress food intake.
Non-RCTAnimal StudyRigorous JournalHighly CitedNon-linear pharmacokinetics of MDMA ('ecstasy') in humans.
MDMA pharmacokinetics show nonlinearity, indicating that small increases in dose can lead to disproportionate rises in plasma concentrations, increasing the risk of acute toxicity in all individuals.
Non-RCTHighly Cited