MDMA
MDMA, commonly known as ecstasy or Molly, is a synthetic empathogen that induces both amphetamine-like stimulation and mild hallucinations. MDMA is used clinically in the treatment of PTSD.
Clinical Dosage
Dosage is usually around 0.75-1.5mg per kg and is often performed in the following stages...[1]
1. Recruitment and medical screening. Start tapering of other medicines if needed.
2. Prep sessions 1 and spaced over 2 weeks.
3. 3rd preparation session. Finish tapering off medications.
4. 1st MDMA assisted session 80mg + 40 mg booster dose (@ 90 minutes).
5. 3 week break with a 90-minute integration session each week.
6. 2nd MDMA session 80mg or 120mg plus half dose booster.
7. 3 week break with a 90-minute integration session each week.
8. 3rd MDMA session 80mg or 120mg plus half dose booster.
9. Last, 3 week break with a 90-minute integration session each week.
10. Final integration session.
Mechanism of Action
Pharmacology
MDMA works by:
- Increasing (↑) dopamine by reducing how it reuptake post release.
- Increasing (↑↑↑) serotonin by reducing how it reuptake post release.
- Increasing oxytocin (neuromodulator) concentration.
Neurophysiology
The change in neural activity coupled with the release of the neurochmicals / neuromodulators above cause a reduction in communication between the medial temporal lobe and the medial prefrontal cortex, which play roles in emotional control. Collectively, these effects work contrary to the patterns observed in individuals experiencing anxiety.[2][3]
Toxicity
Historically there has been one major study showing toxicity of MDMA however it was retracted, this may be a reason why it is often touted as posettially neurotoxicity due to dopamine overload. However, a long term study has shown that there is little evidence of decreased cognitive performance in ecstasy users, save for poorer strategic-self-regulation, possibly reflecting increased impulsivity[4].
Co-administration of caffeine profoundly enhances the acute toxicity of MDMA in rats, as manifested by high core body temperature, tachycardia and increased mortality. In addition, co-administration of caffeine enhances the long-term serotonergic neurotoxicity induced by MDMA[5].
Effects
Short Term
When taken orally, MDMA starts to take effect in about 30 to 45 minutes, with its impact lasting between three to six hours. The experience is often gentler compared to psychedelics and is characterised by feelings of enthusiasm, empathy and trust. MDMA is often described as affiliative which is the opposite to dissociative which is and effect often associated with medicines such as ketamine.
Long Term
MDMA aids in enhancing understanding and management of emotions and coping mechanisms, primarily by augmenting fear memory extinction and rewiring association to trauma leading to decreased amygdala activation. This results in a changed perspective and better processing of traumatic memories. Furthermore, MDMA can modulate fear memory reconsolidation, potentially through effects on oxytocin or activation of serotonin 5HT1B receptors, and improve social behaviors, as observed in animal studies.
Other Effects
Interoception
MDMA has been reported to increase interoception, which is the ability to sense and perceive internal bodily sensations, encompassing awareness of various physiological states. This includes recognizing feelings associated with the functioning of internal organs, such as the rhythm of the heart, breathing patterns, feelings of fullness or hunger, and the activities of the autonomic nervous system that are linked to emotional responses. This is controlled by a part of the brain known as the insular cortex which essentially holds a map of the entire body and how it is feeling this is connected to the amygdala and the strength between these two is what is thought as the underlying mechanistic rationale for ptsd.
Sexual Relationships
It is likely that MDMA increases sexual desire and intensifies orgasm and that dose, ‘set and setting’, and timing relative to MDMA administration make major differences in ability of men to achieve the erectile quality necessary for ejaculation[6].
MDMA has a stronger effect in women
Women are more affected by MDMA's psychoactive effects than males[7]. Women especially have greater perceptual changes, thought disturbances, and fear of loss of body control. In addition, acute adverse effects and sequelae were also more frequent in female than in male subjects. In contrast, men showed higher increases in blood pressure than women.
Coadministration
It is thought that the effects of MDMA might be further potentiated by administration with psilocybin termed a hippie flip[8]. Therapeutically, MDMA is often used first in order to build the therapeutic alliance and increase the patient’s openness to change, leading to enhanced resilience and lowered stress levels. Once further changes were noticed, such as improved self-regulation, less negative self-perception, and increased tolerance to trauma exposure, a psychedelic such as psilocybin was introduced to assist psychotherapy. The deepening of the therapeutic process led to improvement per clinical judgment, without adverse events.[9]
Adverse Effects
MDMA Comedown
There is a wide amount of anecdotal evidence and some scientific evidence[10][11] to suggest that after using MDMA there is an emotional comedown potentially due to prolactin release[12] reported colloquially as "Blue Mondays". However, a recent, low powered study found that there was little evidence for this[13].
References
- ↑ MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial, Jennifer M. Mitchell, Published: 14 September 2023, accessed 4 Dec via https://www.nature.com/articles/s41591-023-02565-4
- ↑ 3,4-Methylenedioxymethamphetamine (MDMA) impairs the extinction and reconsolidation of fear memory in rats. Hake, H. S. et al. Physiol. Behav. 199, 343–350 (2019). http://scholar.google.com/scholar_lookup?&title=3%2C4-Methylenedioxymethamphetamine%20%28MDMA%29%20impairs%20the%20extinction%20and%20reconsolidation%20of%20fear%20memory%20in%20rats&journal=Physiol.%20Behav.&doi=10.1016%2Fj.physbeh.2018.12.007&volume=199&pages=343-350&publication_year=2019&author=Hake%2CHS
- ↑ Oxytocin-dependent reopening of a social reward learning critical period with MDMA. Nardou, R. et al. Nature 569, 116–120 (2019). https://doi.org/10.1038%2Fs41586-019-1075-9
- ↑ Residual neurocognitive features of long-term ecstasy users with minimal exposure to other drugs. Addiction. Halpern JH, Sherwood AR, Hudson JI, Gruber S, Kozin D, Pope HG Jr. 2011 Apr;106(4):777-86. doi: 10.1111/j.1360-0443.2010.03252.x. Epub 2011 Feb 15. PMID: 21205042; PMCID: PMC3053129.
- ↑ Caffeine provokes adverse interactions with 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') and related psychostimulants: mechanisms and mediators. Vanattou-Saïfoudine N, McNamara R, Harkin A. Br J Pharmacol. 2012 Nov;167(5):946-59. doi: 10.1111/j.1476-5381.2012.02065.x. PMID: 22671762; PMCID: PMC3492978.
- ↑ Does MDMA have treatment potential in sexual dysfunction? A systematic review of outcomes across the female and male sexual response cycles. Wexler A, Dubinskaya A, Suyama J, Komisaruk BR, Anger J, Eilber K.. Sex Med Rev. 2023 Oct 26:qead046. doi: 10.1093/sxmrev/qead046. Epub ahead of print. PMID: 37888490.
- ↑ Gender differences in the subjective effects of MDMA. Psychopharmacology (Berl). Liechti ME, Gamma A, Vollenweider FX. 2001 Mar 1;154(2):161-8. doi: 10.1007/s002130000648. PMID: 11314678. Accessed on 10 May 2023 via: https://pubmed.ncbi.nlm.nih.gov/11314678/
- ↑ Co-use of MDMA with psilocybin/LSD may buffer against challenging experiences and enhance positive experiences. Zeifman, R. J., Kettner, H., Pagni, B. A., Mallard, A., Roberts, D. E., Erritzoe, D., Ross, S., & L., R. (2023). Scientific Reports, 13(1), 1-11. https://doi.org/10.1038/s41598-023-40856-5
- ↑ Therapeutic role of psilocybin and 3,4-methylenedioxymethamphetamine in trauma: A literature review. Fonseka LN, Woo BK. World J Psychiatry. 2023 May 19;13(5):182-190. doi: 10.5498/wjp.v13.i5.182. PMID: 37303932; PMCID: PMC10251361.
- ↑ Safety pharmacology of acute MDMA administration in healthy subjects. J Psychopharmacol 31: 576–588. Vizeli P, Liechti ME. (2017) Accessed on 20 Nov 2023 via https://pubmed.ncbi.nlm.nih.gov/28443695/
- ↑ Gender differences in the subjective effects of MDMA. Liechti ME, Gamma A, Vollenweider FX. (2001) Psychopharmacology 154: 161–168. Accessed on 20 Nov 2023: https://pubmed.ncbi.nlm.nih.gov/11314678/
- ↑ Ecstasy (MDMA) mimics the post-orgasmic state: impairment of sexual drive and function during acute MDMA-effects may be due to increased prolactin secretion. Passie T, Hartmann U, Schneider U, Emrich HM, Krüger TH. Med Hypotheses. 2005;64(5):899-903. doi: 10.1016/j.mehy.2004.11.044. PMID: 15780482.
- ↑ Debunking the myth of 'Blue Mondays': No evidence of affect drop after taking clinical MDMA. J Psychopharmacol. 2022 Mar;36(3):360-367. doi: 10.1177/02698811211055809. Epub 2021 Dec 13. . Ben Sessa, Jacob S Aday, Steve O'Brien, H Valerie Curran, Fiona Measham, Laurie Higbed, David J Nutt. https://pubmed.ncbi.nlm.nih.gov/34894842/