therapeutic effects of mdma annie chen cynthia le daniel hagan mustafa nasr...
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Therapeutic effects of Therapeutic effects of mdmAmdmA
Annie ChenCynthia Le
Daniel HaganMustafa Nasr
(3,4-Methylenedioxymethamphetamine)
Table of ContentsTable of ContentsMechanism of Action
Therapeutic Neurobiological Mechanism
Neurotoxicity
Long term Serotonergic Changes
Structural Changes in Serotonergic Axons
Role of Oxidative Stress in Neurotoxicity
Safety Assessment in Clinical Studies
Therapeutic Potential
Therapeutic Benefits
Therapeutic Dangers
History of Therapeutic Use of MDMA
Role of Mental Set
Results and Conclusion
Therapeutic Use of MDMA Today
MDMA-PTSD U.S. Pilot Study
Mechanism of ActionMechanism of Action
Primarily serotonergic, but also effects norepinephrine and dopamine
Enters pre-synaptic cell via monoamine transporters
Inhibits vesicular monoamine transporter
Releases monoamines by reversal of respective transporters through phosphorylation
Also acts as a weak 5-HT, and 5-HT2 agonist
Causes indirect oxytocin secretion by stimulating serotonin system
Inhibits rate-limiting enzyme for 5-HT synthesis; typtophan hydroxylase
MDMA (Ecstasy)MDMA (Ecstasy)MDMA in synaptic cleft
Therapeutic Therapeutic Neurobiological Neurobiological
MechanismMechanismIncreased oxytocin levels strengthen alliance between patients and therapist
Decrease in amygdala activity with an increase in ventromedial prefrontal activity improves emotional regulation and decreases fear and avoidance
Increase in norepinephrine and cortisol levels facilitates emotional engagement and extinction of learned fear associations
NeurotoxicityNeurotoxicityAppears to have same risk for neurotoxicity as other psycho-stimulants (i.e. methamphetamine)
Very modest risk of acute toxicity in controlled environment
Studies with animals have shown that MDMA can decrease brain-functions that rely on serotonin on a long-term basis ( >7 days)
However, it is unclear what effect this has on the animals
No studies have investigated whether MDMA causes neurotoxicity that only becomes apparent with aging
Longterm Serotonergic Longterm Serotonergic ChangesChanges
Decreased brain concentrations of serotonin and its metabolite 5-HIAA
Decrease in density of SERT (serotonin re-uptake transporter)
Is this down-regulation? Or have serotonergic axons been permanently lost or damaged?
Down regulation suggests an active adaptation to the increase in serotonin from ecstasy (MDMA) while axonal loss suggests true damage
Structural Changes to Structural Changes to Serotonergic AxonsSerotonergic Axons
Looking at the structure of serotonergic axons in animals exposed to MDMA clearly indicates axonal loss
Slices of MDMA exposed animal brain tissue in which 5-HT has been stained show irregular swelling and fragmentation of fine serotonergic axons
Swelling suggest damage of axons and this can be proven by measuring the movement of compounds between brain regions connected by serotonergic axons
Role of Oxidative Role of Oxidative Stress in NeurotoxicityStress in Neurotoxicity
Highly reactive chemicals call free radicals damage neural molecules through reduction and oxidation. These reactions alter the ability of neural cells to carry out their normal functions
MDMA has been shown to increase oxidative stress in the brain by two separate methods
Antioxidants are molecules that react with free-radicals to create harmless molecules
Role of Oxidative Role of Oxidative Stress in Neurotoxicity Stress in Neurotoxicity
cont...cont...Mice given extreme doses of antioxidants (or genetically altered to have naturally elevated levels of antioxidants) such as vitamin C and alpha-lipoic acid show no signs of neurotoxicity when given a normally neurotoxic regiment of MDMA (the dose of MDMA and vitamin C are very high)
Sustained effects of MDMA may deplete neuronal energy sources and their ability to deal with oxidative stress
Both MDMA and Dopamine can be metabolized into highly reactive molecules
Safety Assessment in Safety Assessment in Clinical StudiesClinical Studies
Range of psychoactive, but non-neurotoxic MDMA closes appears small in most animals
However, the dosage and frequency of administration can be kept to the minimum required
Furthermore, methods for reducing or blocking neurotoxicity in animals can be employed and likely reduce neurotoxicity at least to some degree in humans
Safety Assessment in Safety Assessment in Clinical Studies cont...Clinical Studies cont...
Methamphetamine has shown to exhibit at least the same neurotoxicity as MDMA, but the FDA still approves of methamphetamine
SSRI’s block SERT and inhibits the function of MDMA
When given 3-4 hours after a neurotoxic regiment of MDMA, several SSRI’s (such as paroxotine, fluoxetine and citalopram) can block neurotoxicity in rodents. Although human-trials have not been conducted it is likely that they have a similar effect in humans.
Therapeutic PotentialTherapeutic Potential
Physical and Psychological distress of terminal cancer patients
Treatment of PTSD (post-traumatic stress disorder) caused by:
Sexual assault
War
Violent crimes
TherapeutTherapeutic ic
BenefitsBenefitsHelps break down boundaries
in communication
Especially useful for patients who are aggressive, defensive
and unwilling to “open up”
Increased feelings of empathy
Increased feelings of acceptance
Depersonalization; loosening of ego and boundaries
Feelings of tranquility and peace
TherapeutiTherapeutic Dangersc Dangers
Chance of psychological dependence
Possible adverse effects
‣increased body temp
‣increased heart rate and blood pressure
‣muscle tension
‣jaw clenching nausea
Impairment of episodic and working memories and
attention
History of History of Therapeutic Therapeutic
Use of MDMAUse of MDMAGreer & Tolbert
‣MDMA assisted
‣psychotherapy sessions from
‣1980 to 1985
‣80 patients total
‣screening criteria and informed consent
‣mental set and psychological preparation emphasized
Role of Role of Mental SetMental Set
Set includes expectations, motivations and intentions of
individual in regard to the session
Mental set both patient and therapist important
Goal of developing more compassionate attitude was easily
achieved by MDMA-assisted therapy
Relief from chronic symptoms and behavior problems greater when such
change in attitude occurred
Approached sessions more as sacred rites of passage than
conventional therapy sessions
Results & Results & ConclusionConclusion
ssMDMA seems to decrease fear
response to perceived threat to patient’s emotional integrity
Leads to corrective emotional experience
Diminishes pathological effects of previous traumatic experiences
Acquisition of effective skills for communicating feelings to family
members
Psychological benefits were lasting up to a 2-year follow-up for
most patients
Therapeutic Use of Therapeutic Use of MDMA TodayMDMA Today
Currently only one FDA & DEA approved medical study on MDMA (Schedule 1 drug)
MAPS (multidisciplinary association of psychedelic studies) is studying whether MDMA-assisted psychotherapy has potential to heal traumas caused by sexual assault, war, violent crime and other causes
In the middle of a 10 year, $10 million plan to make MDMA a government-approved prescription medication
MDMA-PTSD U.S. Pilot MDMA-PTSD U.S. Pilot StudyStudy
1st ever protocol evaluating MDMA’s therapeutic applications in clinical trials
Randomized, double blind and placebo controlled
21 subjects with treatment resistant PTSD
MDMA-assisted psychotherapy produced statistically significant improvements in PTSD symptoms
Difference between 2 groups was immediate and maintained throughout the time period
SourcesSourceshttp://www.maps.org/research/mdma/
http://www.macalester.edu/psychology/whathap/ubnrp/mdma/therapeutic.html
http://www.lycaeum.org/research/researchpdfs/1998_greer_1.pdf
Peroutka, Stephen J. Ecstasy: the Clinical, Pharmacological, and Neurotoxicological Effects of the Drug MDMA. Boston: Kluwer Academic, 1990.
http://www.science.smith.edu/departments/Biochem/Chm_357/Articles/ecstasy%20toxicity.pdf
http://www.erowid.org/library/books/ecstasy_complete.shtml
http://www.idmu.co.uk/ecstasy-information/
http://www.springerlink.com/content/9rvc16g5hgmdg6wb/