MDMA Supplements

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Background[edit]

Do I need to take supplements with MDMA?

No. However, I would advise any family members of mine who were planning on taking MDMA to use supplements each time, and to follow the other harm reduction methods on MDMA Safety Enhancement and Enjoyment Amplification using Supplements and Other Methods.

Why would you advise a family member to take supplements with MDMA?

If supplements can protect against MDMA damage (if it happens) at a low cost, then the cost-benefit ratio for supplements is excellent.

I believe the best rationale for taking supplements with MDMA is that supplements may reduce the risk of or prevent "losing the magic" with MDMA use over time. This is hypothetical. We do know supplements can prevent MDMA tolerance in rats.

"By 2021 MAPS hopes to have MDMA approved by the FDA for treatment of PTSD. After that, you may one day step into a couples counseling session and take MDMA with your partner to strengthen your marriage, or to repair a relationship with your child.

If you've "lost the magic" of MDMA by then you may be forever unable to use a vital treatment method."

MDMA Supplement Table[edit]

Supplement Recommendation Purpose Research Possible schedule with MDMA Price per event Tmax Elimination half-life Dosage used in human research
Alpha Lipoic Acid (ALA) Strongly recommended Neurotoxicity minimization Alpha-lipoic acid prevents MDMA-induced neurotoxicity. Rat study used 100mg/kg twice a day for 2 days.

Proposed: 300-mg ALA with MDMA dosing, then every hour after that until 7 h post dose (total 2.4-g)

See below for Na-RALA comparison.

1 h for 600-mg ALA, 14 min for 600-mg Na-RALA 0.6 h for 600-mg ALA, 14 min for 600-mg Na-RALA 600-mg ALA, Up to 2400-mg/day
Acetyl-L-carnitine (ALCAR) Strongly recommended Neurotoxicity minimization Acetyl-L-carnitine provides effective in vivo neuroprotection over MDMA-induced mitochondrial neurotoxicity in the adolescent rat brain. Rat study used "a single i.p. injection of 100 mg/kg ALC."

500-mg 3 h before and then every 2 h until 5 hours after dosing (2.5-g)

$23.26 for 200 x 500-mg 3.1 h for 500-mg 4.2 h for 500-mg 630-2,500-mg of ALCAR
Electrolytes / Isotonic fluids Strongly recommended, especially important for females Reduced hyponatremia risk MDMA impairs response to water intake in healthy volunteers

Sex differences in the effects of MDMA (ecstasy) on plasma copeptin in healthy subjects.

Ideally we want to consume isotonic fluids (i.e. ~290 milliOsmol/L).

Perhaps 1/4 - 1/2 sodium containing electrolyte packet with 250-ml water per hour, or 250-ml electrolyte beverage per hour (Gatorade has about 110-mg sodium per 250-ml, coconut water has 25 to 50-mg per 250-ml)

$12.95 for 36 Propel Powder packets with 210-mg sodium

$1.08 for 3

Lasts for 12 sessions

Ubiquinone (Co-Q10) Encouraged Neurotoxicity minimization Evidence for a role of energy dysregulation in the MDMA-induced depletion of brain 5-HT. Rat study used 100-microM, roughly 300-mg/kg "perfused into the striatum beginning 2 h before the first MDMA or vehicle injection and continuing until 6 h after the last drug injection."

800-mg 6 h before, 800-mg at same time as MDMA, and 800-mg 6 h after MDMA (2.4-g)

$13.14 for 120 x 100-mg

$2.63 for 24

Bottle of 120 lasts for 5 people/MDMA sessions

6.5 h for 100-mg 33 h for 100-mg 90-mg once daily, up to 3,600-mg daily
Nicotinamide Encouraged Neurotoxicity minimization Evidence for a role of energy dysregulation in the MDMA-induced depletion of brain 5-HT. Rat study used 1-mM, roughly 400-mg/kg "perfused into the striatum beginning 2 h before the first MDMA or vehicle injection and continuing until 6 h after the last drug injection."

500-mg 1 h before, 1 h after, 3 h after, 5 h after, 7 h after (2.5-g)

$26.89 for 100 x 500-mg

$1.34 for 5

Bottle of 100 lasts for 20 people/MDMA sessions

45 min for 500-mg 1, 2 ~2 h for 500-mg 1, 2 1 g+, <3 g/day
Vitamin E Encouraged Neurotoxicity minimization d-MDMA during vitamin E deficiency: effects on dopaminergic neurotoxicity and hepatotoxicity. Average American intake of 6.5-mg/day from food.

Beginning 7 days before MDMA dose, 400-IU daily, including 400-IU on the morning of MDMA dose (8 total).

If this is impractical, perhaps a single dose of 1200-IU on the morning of MDMA dose day.

$11.10 for 100 x 400-IU

89c for 8

Lasts for 12 sessions

13 h for 800-mg of α-tocopheryl (1200-IU) 73 h for 800-mg of α-tocopheryl In this study, 320-mg/480-IU per day saw antioxidant benefits, <= 1600-IU
Ascorbate (Vitamin C) Encouraged Neurotoxicity minimization Ascorbic acid prevents MDMA-induced hydroxyl radical formation and the behavioral and neurochemical consequences of the depletion of brain 5-HT. In rat study: "100 mg/kg, i.p. every 2 h for a total of 5 injections" "in which ascorbic acid was given 1 h before each MDMA injection and 1 h after the last MDMA injection." A rough human conversion might be 7-g vitamin C every 2 h, though you might experience diarrhea at this dosage (e.g. see this paper).

Proposed: 1-g vitamin C 6 h before MDMA dose, 5 h before, then resuming 2h after dose and hourly until 6 h post MDMA dose (total of 7-g). Dosage gap (4 h sufficient) to prevent any gastrointestinal acidification which may hypothetically slow the speed of MDMA absorption, unclear if it would impact onset of effects though. I would recommend 7-g every 2 hours if I there wasn't a risk of diarrhea. Perhaps you could try dosing vitamin C on a non-MDMA day to see how your body tolerates larger doses.

$13.83 for 250 x 1000-mg

39c for 7

Bottle lasts for 35 sessions/people

4 h for 250-mg in smokers 24 h for 250-mg in smokers
Cysteine - Neurotoxicity minimization Effect of ascorbate and cysteine on the MDMA-induced depletion of brain serotonin (1996).
Magnesium Use if you experience jaw clenching Bruxism (jaw clenching) Anecdotal 2-4 tablets on the morning of $15.37 for 240

26c for 4 caps

Lasts for 60 sessions

5-HTP Use if you experience a come down "Come down" reduction Anecdotal Anecdotal and hypothetical concerns around serotonin syndrome if co-administered. No literature, but the cautious method would be to avoid taking 5-HTP perhaps 24 hours before or after taking MDMA.

Dosing regimen[edit]

Timing Recommended supplements Comprehensive supplements (includes "Recommended")
Daily for 7 days prior to MDMA dose - 400-IU Vitamin E
6 h before dose - 800-mg Co-Q10, 400-IU Vitamin E
5 h before - -
4 h before - -
3 h before 500-mg x ALCAR 500-mg x ALCAR
2 h before - -
1 h before 500-mg x ALCAR 500-mg x ALCAR, 500-mg x Nicotinamide
With MDMA dose 300-mg x ALA 300-mg x ALA, 800-mg x Co-Q10
1 h after dose 300-mg x ALA, 500-mg x ALCAR 300-mg x ALA, 500-mg x ALCAR
2 h after 300-mg x ALA 300-mg x ALA, 500-mg x Nicotinamide
3 h after 300-mg x ALA, 500-mg x ALCAR 300-mg x ALA, 500-mg x ALCAR
4 h after 300-mg x ALA 300-mg x ALA, 500-mg x Nicotinamide
5 h after 300-mg x ALA, 500-mg x ALCAR 300-mg x ALA, 500-mg x ALCAR
6 h after 300-mg x ALA 300-mg x ALA, 800-mg x Co-Q10, 500-mg x Nicotinamide
7 h after 300-mg x ALA 300-mg x ALA
8 h after - 500-mg x Nicotinamide

During your MDMA session, consume only electrolyte containing fluids (sugar free gatorade, coconut water, Propel powder packets in water, etc). Limit fluid intake to 500-ml/hour if dancing, or 250-ml/hour if not highly active.

Try and keep your body temperature within normal range. If dancing, cool off each hour or more frequently.

See RollSafe for a more user friendly presentation of this material.

Other important notes

Don't dose if you've taken any MAOIs in the past 14 days.

Don't take 5-HTP within 24 hours of dosing.

Look over the list of cautions on this page and make sure none apply to you: MDMA Safety Enhancement and Enjoyment Amplification using Supplements and Other Methods.

Vitamin C has been left out, add in at your own tolerance (Vitamin C at high doses can upset your GI system, depending on the person).

Last minute purchasing options (grocery stores, Instacart/Amazon Prime Now)[edit]

If you're using MDMA within a few hours and need to purchase supplements from a store, this is an option.

The simplest option would be to purchase ALA (not Na-RALA) and ALCAR. Most grocery stores or health food stores should carry both of these. The price will be higher than purchasing online.

You could use a service like Instacart or Amazon Prime Now to have the groceries delivered within a few hours if you can't leave the house.

Look for 300-mg ALA, and get a bottle with 8 pills per person (600-mg is okay, and then you could dose half as often, however smaller, more frequent doses are hypothetically better). Look for 500-mg ALCAR, and get a bottle with 5 pills per person.

FAQ[edit]

How can we calculate human dosages from rat studies?[edit]

We don't really know. It's speculative. Rat studies use high supplement dosages because they want to increase the chance of a statistically significant effect.

Matthew Baggott: "I think we don't know doses/concentrations needed to start getting protection for any of these supplements and most are more likely to helpful than harmful."

The short answer is we cannot calculate human dosages, in supplements with no downsides we might encourage higher doses as they are more likely to help than hurt and most supplements are pretty cheap.

ALA vs Na-RALA[edit]

Data[edit]

Pharmacokinetics, Metabolism, and Renal Excretion of Alpha-Lipoic Acid and Its Metabolites in Humans [1] [2] [3]

"The bioavailability, Cmax, and AUC values were decreased by the coingestion of food (Gleiter et al., 1996)."

200-mg racemic alpha-lipoic acid AUC data: 24.6+-7.8 for R(+)-alpha-lipoic acid and 15.0+-5.4 mcg min/mL for S(-)-alpha-lipoic-acid

200-mg racemic alpha-lipoic acid AUC 46.82 +- 21.46 mcg min/mL (total ALA, not separated by isomer)

600-mg racemic alpha-lipoic acid AUC 148.08 +- 58.67 mcg min/mL (total ALA, not separated by isomer)

If we assume the R/S ratio from the 200-mg racemic mixture holds, then the 600-mg would have AUC for R(+) of ~90 mcg min/mL

The Plasma Pharmacokinetics of R-(+)-Lipoic Acid Administered as Sodium R-(+)-Lipoate to Healthy Human Subjects. [4]

600-mg oral Na-RALA total (including both R and S) AUC 441.6 mcg min/mL

Pharmacokinetics of different formulations of tioctic (alpha-lipoic) acid in healthy volunteers. [5]

600-mg oral ALA total (including both R and S) average AUC 3131.45 ng × h/g (199.16 mcg min/mL)

Based on the above limited data, 600-mg ALA seems to give a total (R & S) AUC of about 3 times lower than 600-mg Na-RALA. 600-mg ALA hypothetically gives an R(+) AUC of ~5 times lower than 600-mg Na-RALA.

$20.86 for 180 x 600-mg ALA gives a cost of 11.6c per 600-mg ALA. $16.59 for 60 x 100-mg Na-RALA gives a cost of $1.659 per 600-mg Na-RALA. This Na-RALA is 14.3x more expensive than the ALA in question.

Conclusion[edit]

Na-RALA is 14.3x more expensive in the above comparison, and the more generous comparison gives it an AUC that is ~5X higher than ALA.

ALA is recommended vs Na-RALA (RALA) because it is more cost effective.