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"Ask Dr. Mercury: 'Mixing Wellbutrin and ecstasy?'
DanceSafe proudly introduces a new monthly column, ‘Ask Dr. Mercury’ where common questions about drug use and its interactions with the mind and body have a chance to be answered by an expert in a public forum.
Who is Dr. Mercury? Dr. Mercury is a medical doctor trained in neurology and psychiatry currently engaged in substance abuse research.
Every month Dr. Mercury will answer one question of the hundreds we are e-mailed or are posted in the e-board .
The first question for Dr. Mercury involves mixing Wellbutrin and ecstasy comes from ‘Sam’ and is one we have been asked a lot recently . To see how to submit a question to Dr. Mercury, please read details at the end of this column.
“I am considering taking ecstasy but I recently started taking 300mg daily of Wellbutrin for depression and am worried about the side effects of mixing the two. I have seen a lot of information on using other anti-depressants and ecstasy, but Wellbutrin, as I understand, works different than other anti-depressants. Does taking Wellbutrin and ecstasy pose a serious risk? Should I stop using Wellbutrin a day or so before using ecstasy? Any advice would be great, thx.” -- Sam
Sam--
I have to congratulate you on your prudence. You are wise to learn as much as you can before mixing any drugs in untried combinations, particularly psychoactives. But I’m sure you know better than to think I could ever tell you that the combination is safe! No, no—stay home, young man. And eat your fruits and vegetables!
But what you are asking is actually several questions. Let me list them, and do my best to answer each in turn:
1. What are the potential risks of mixing bupropion (the generic name for Wellbutrin, which is how I shall refer to it) and MDMA (Ecstasy)?
2. What is the mechanism of action of bupropion, and will it kill the Ecstasy, strengthen it or what?
3. Would a one- or two-day “washout” period lessen either of these effects?
We can approach this problem in a couple of ways. The first is to think a little about the pharmacology of the two substances and see if we can make a reasonable guess at what might happen should we mix the two drugs. And the second—the more practical but less reliable approach—is to see if we can find any described cases of people running into trouble mixing the two.
As you know, the human brain is a hugely complicated neural network that generates thought, emotion and behavior through an ever-changing pattern of electrical impulses, similar to those that run through the microprocessor of your computer. What your brain has that your computer does not, however—and the reason why we can understand a joke, walk up a flight of stairs and beat all but the best chess-playing machines—is a system of chemicals called neurotransmitters that modulate the flow of electrical impulses and give the entire system considerably more flexibility than a machine ever has. There are about a hundred different neurotransmitters; about sixty have been discovered, and six or so can be manipulated pharmacologically. Ninety percent of your synapses are simply excitatory (glutamine) or inhibitory (GABA), the fundamental black-and-white yin-yang that underlies our existence. Three of the hundred neurotransmitters are special, however. Serotonin, norepinephrine, and dopamine, which spring from a relatively tiny collection of cells in your brainstem, project to all corners of your brain and add the color to your existence.. And it is for that reason that almost all psychiatric drugs are targeted towards one or more of the three.
Antidepressants such as Prozac, Luvox, Zoloft, Paxil, Celexa, and Lexapro are called SSRIs, or “selective serotonin reuptake inhibitors”. By blocking the pump that clears serotonin from the synapses, these drugs are able to cause prolonged high levels of serotonin. The body responds after a couple of weeks by decreasing the number of serotonin receptors that detect the serotonin, and for reasons not entirely clear, this causes an improvement in mood. MDMA affects the serotonin reuptake pump as well, not by blocking it, but by making it spin in reverse, dumping a flood of serotonin—about 80% of your total supply—into the synapse and causing an immediate mood elevation. Not surprisingly, MDMA and all the drugs I just mentioned interact with each other, although it might surprise you to know that generally antidepressants trump MDMA every time; they all bind to the serotonin pump more strongly and will displace MDMA if it is present.
You are correct that bupropion acts via a slightly different mechanism, however—it is not an SSRI but an “aminoketone”. Rather than affecting serotonin, it targets the other two colorful neurotransmitters I mentioned, norepinephrine and—less strongly—dopamine. Norepinephrine is the neurotransmitter most strongly associated with arousal and alertness, and it is for this reason that first-time users of bupropion complain that it feels “speedy”, akin to drinking two or three cups of coffee, before they get used to it. Unfortunately, taken further this can also lead to the big worrisome side effect of bupropion—seizures. Generally seizures do not occur at doses lower than 450 mg/day, or in the absence of something else that might lower one’s seizure threshold, such as an electrolyte imbalance (as can occur in bulimics) or a head injury. In doses less than 300mg a day, your seizure risk is one in a thousand; in doses between 300mg and 450mg a day, that rises to four in a thousand. Not a lot, but not nothing, either. What about combining it with MDMA? Seizures have certainly been reported from use of Ecstasy, although the incidence pales in comparison with that reported from other stimulants such as cocaine or methamphetamine. Often the seizures are actually from a metabolic imbalance such as low sodium, or it turns out that the Ecstasy involved was actually not MDMA at all, but rather an adulterant such as PMA . Still, you never know what you’re getting, and we have to assume that Ecstasy can lower the seizure threshold in those susceptible to it, and that could be you. So don’t come crying to me if it happens, eh?
Is a washout period worth it then? The half-life of bupropion is fairly short—21 hours—which is why it is usually given twice a day. Not much will be left in your system if you stop for a couple of days, and unlike some antidepressants such as Effexor or Paxil that have a discontinuation syndrome that will kick your ass, bupropion is easy to stop. However, it has three active metabolites that accumulate to high levels and take much longer to leave the body—hydroxybupropion has a half-life of 20 hours, erythrobupropion 33 hours and threohydrobupropion 37 hours. We can easily calculate how much is left after a drug holiday:
Drug: 24h 48h 72h
__________________________________________________ ______
bupropion 45% 20% 9%
hydroxybupropion 43% 19% 8%
erythrobupropion 60% 36% 22%
threohydrobupropion 63% 40% 25%
Even after three days, there’s still a substantial amount of stuff floating around in your bloodstream, which is no doubt why nobody seems to have any problems stopping it for a day or two. The active metabolites are actually what’s thought to be responsible for the unpleasant side effects of the medication, but whether they’re responsible for causing the seizures as well, I don’t know!
So much for theory. Now, are there any actual cases reported of people who have tried bupropion and Ecstasy, or who have run into difficulties with the combination? Now, I couldn’t find out how many people have been given bupropion in the USA, but in the UK the figure is 419,000, or 0.7% of the population. Given 2.5 million Ecstasy users in the same country, odds are that 17,000 people in the UK alone have tried the combination, with probably many more in this country. A search of the scientific literature reveals plenty of case reports of people developing serotonin syndrome or other adverse side effects from combining Ecstasy with antidepressants such as Zoloft, or monoamine oxidase inhibitors, or even nothing at all, but none from combining it with bupropion. An anonymous source in the government who has been collecting cases of Ecstasy/antidepressant interactions and who helps Dr. Mercury from time to time drew a blank when I asked about bupropion. That no proof it’s safe, of course, but the lack of tombstones is an indication that it’s probably not a fatal combination. And as far as interfering with the subjective effects of Ecstasy, a few of those 17,000 have reported back that it does not, which matches what we might predict from the pharmacology.
So in summary, I would say this. There have been no reported cases of adverse interactions or death from a combination of bupropion and MDMA. Bupropion should not diminish the strength of the experience. Discontinuing the bupropion for a few days should be safe but is probably won’t make a difference, and if you do so be careful not to start right up again at the full dose—ask your doctor for a recommendation regarding restarting it. I can’t promise that you won’t have a bad reaction, but you’re more likely to feel the “speedy” effects of combining two drugs with stimulant effects than you are to have an adverse effect such as a seizure or serotonin syndrome.
I hope this helps!
--Dr. Mercury
To submit a question to Dr. Mercury, please send an e-mail to DrMercury AT DanceSafe.org – we will remove all personal information such as full name, geographical information and other identifying markers in your question. We attempt to answer all serious questions about drug use in a timely fashion even if the question is not picked to be answered by Dr. Mercury. You can also post your question on our e-board for a peer-based response and discussion.
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