Illegal Drugs and the Potential for Therapeutic Use with an Emphasis on Ecstasy

Ecstasy, or MDMA, has been around for nearly a century, and it’s popularity in the media has waxed and waned for the past 30 years or so as the issues around it come and go. It is important to know where ecstasy came from and all the places it has been in order to better understand where it is going. And due to its potential for therapeutic benefits, ecstasy is definitely going somewhere…

MDMA (3,4-methylenedioxy-N-methylamphetamine) was first synthesized in 1912 by a scientist at Merck, Anton Köllisch. It was never meant to be anything special, just an intermediate product necessary for making hydrastinine, and remained in the shadows of chemistry for years. Max Oberlin used MDMA in 1927 to mimic the effects of adrenaline in animals, because MDMA acts as a stimulant and has some similar physiological effects 1. But again, MDMA was not considered something unique in itself, but was instead considered with regard to another, more important, drug.

Nonetheless, MDMA showed up in the lethal-dose studies conducted by the US ARMY in the 1950s, and later became a recreational drug 1. In the 60’s MDMA became known as a potent “love drug” 1, good for creating a sense of empathy and deep introspective thought, as well as heightening the senses. Alexander Shulgin experimented with ecstasy himself in the 70s, along with hundreds of other drugs 1. His experiences while on the drug have been written about in his book “Pihkal” 2. Because of the effects of the drug, Shulgin recommended it to his psychotherapist friend Leo Zeff for therapeutic use with his patients 1. It was at this point that the effects of ecstasy we most likely identified as beneficial in a clinical setting.

But the gaining prevalence of the drug did not stop there. It continued to become more popular for its effects, and seeped into the party culture. Initially a drug used in elite nightclubs, ecstasy found its way into gay clubs and then hit the rave scene as the drug of choice. After it became popular as an all-night dancing drug within raves, ecstasy became a common street drug in the US and was subsequently banned in 1985 1.

Ecstasy was classified in 1985, and remains today, a schedule I controlled substance under the Controlled Substance Act. The criterion for a schedule I drug include a high potential for abuse, a lack of currently accepted medical use in treatment in the United States, and a lack of accepted safety for use of the drug under medical supervision 1. Despite the testimony of several practitioners that ecstasy had proven highly effective in clinical settings (at least anecdotally) 1, the drug received the strictest of all substance classifications and is illegal even in medical settings 3.

Effects on mind, body, and brain

It is the mental effects of ecstasy that led to its use both therapeutically and as a party drug or street drug. The term ecstasy in ancient Greek means “to be or stand outside oneself; a removal to elsewhere” 4. And the mental effects of the drug seem to be just that. In addition to a sense of extreme euphoria, users taking ecstasy describe their experiences as being highly reflective and introspective. They are willing to think about things, including themselves, in new and deeper ways, often assigning meaning to previously meaningless observations 1. Thus in this way they are able to “stand outside” themselves and reflect on experiences in a way not possible without the aid of the drug. Patients can consider a traumatic past event more clearly when not hindered by their personal emotional experiences associated with it, such as guilt or fear. In Shulgin’s book “Pihkal,” he describes the interaction of a patient taking ecstasy and the clinician. The patient’s mother had died while giving birth to her, and she had lived her entire life with the guilt of having been given life at the cost of another’s life. She had not made progress with other practitioners, but once on ecstasy asked “Is it okay to be alive?” The response “You bet your sweet ass…” and the uninhibited state caused by the drug were enough to lead to the patient’s own affirmation and come to peace with her personal experience 2.

Along with these mental effects, and also beneficial in a therapeutic setting, users experience an abatement of hostility and insecurity 1. In this way, too, they are better able to think about experiences in novel ways. For example, one woman has publicly described her experience of taking ecstasy with her husband, who was diagnosed with terminal cancer. Although they have fought continuously since his diagnosis, while under the influence of ecstasy they were able to openly discuss all the problems they were having and came to terms with each issue that had arisen with the cancer. Without the hostility and negative emotions that had surrounded their previous arguments, they were able to discuss and consider the issues more effectively. According to her they achieved a sense of peace while on the drug, and never fought again 5.

There are several other mental effects of ecstasy while under the influence of the drug. All of them are positive and capable of contributing to mental healing and effective psychotherapy sessions such as the ones above. Profound feelings of intimacy and empathy for others 1 can help someone feel connected, to their therapist or someone else. Ability to discuss normally anxiety-provoking topics easily 1 can promote reparative discussion with a professional or someone of a close relationship. Helping to aid personal growth and understanding are a strong sense of inner peace and self-acceptance, as well as insightfulness and mental clarity 1. And while enhancement of the senses 1 may not play an important role in the psychotherapy setting, when combined with the other effects of the drug, the experience of heightened senses adds to the feeling of awareness and is a pleasant addition to the overall experience of being on ecstasy.

As with any drug, ecstasy has undesired physiological side-effects which can become dangerous in the wrong person or the wrong set of circumstances. The most notable of these physiological side effects is an impairment in the body’s ability to regulate temperatures. One study found that rats given MDMA and placed in a cold environment had a lower body temperature than control rats in the same environment. Similarly, rats placed in a warm environment had a higher body temperature if they had exposure to MDMA than those that were not given the drug 5. This is not likely to be a highly problematic symptom in general. However, when considering the typical environment of use, an inability to regulate temperature becomes highly relevant. When ecstasy is taken as a party drug, the user is often in a hot, crowded environment- a party. Dancing also causes an increase in body temperature, thus dancing all night at a crowded rave can greatly amplify the effects of ecstasy on body temperature. Hyperthermia is one of the leading causes of emergency room visits and deaths of individuals taking only ecstasy 6.

Dehydration can also become a serious problem for individuals who exert energy dancing longer than they would be able to if they weren’t on the drug 6. This side effect is again of particular application to those taking ecstasy as a party drug in a hot, congested environment. Because of the knowledge that overheating and dehydration can be serious or even fatal for ecstasy users, people taking the drug at raves may overcompensate by drinking vast amounts of water. MDMA has anti-diuretic properties, which means that any water taken in is retained in the body longer 6. Occasionally, ecstasy users can suffer from rare, but severe, hyponatremia. When an individual consumes too much water without expelling it via urination or sweat, the body’s salt-to-water ratio can become too low, resulting in this dangerous condition 6.

It should be noted that aside from the MDMA itself, the primary factor in each of these potentially harmful physiological conditions is the environment of a party or rave. While all users of ecstasy experience the rush of energy that comes from its properties as a stimulant, only the users in a party setting are likely to expend that energy in a potentially deleterious manner. That is to say that, even though the patient described from “Pihkal” ran down a hill in the backyard of the clinician upon realizing it was okay for her to be alive, she did not continue to run up and down the hill for the following several hours while under the drug’s influence. She sat and talked about her past and experienced the positive mental effects of ecstasy without exposing herself to the risks of the negative physiological effects 2. Due to the strong role of environment in determining the impact of the physiological effects discussed thus far, it is not likely that these effects would create complications for a patient in a therapy setting.

There is however an additional set of negative physiological side effects of ecstasy that could be severe regardless of the environment. Because ecstasy is a stimulant, MDMA increases the blood pressure and heart rate in those who take it 6. This is not generally problematic in a healthy individual, but it can be life-threatening in individuals with pre-existing conditions 6. For this reason, MDMA should not be taken by individuals with high blood pressure, heart defects, or other heart conditions as the risk of complication would be much higher. Thus far, this is the only well documented and un-refuted physiological risk of MDMA, although it has been debated for several years whether ecstasy has other lasting physiological effects on the brain.

The immediate role of MDMA on the serotonin pathway has been well documented. When ecstasy enters the synapse between a presynaptic cell that releases serotonin and a postsynaptic cell with receptors for serotonin, the drug is readily taken into the presynaptic cell via the serotonin re-uptake mechanism. The re-uptake transporters have a higher affinity for MDMA than for serotonin neurotransmitters, and once the transporters take the MDMA into the cell their function is reversed. The transporters then expel serotonin out of the presynaptic cell into the synapse, where the serotonin neurotransmitters bind with receptors to activate the postsynaptic cell. Because the transporters’ function is reversed, they do not remove the serotonin from the synapse, and it continues to bind repeatedly to the postsynaptic cell 7. It is the release of serotonin that is most likely responsible for the reduction of anxiety and defense mechanisms 2.

It is also known that MDMA stimulates the dopamine reward system 7, although this activity occurs to a much lesser degree than the serotonin pathway activation. It is possible that the involvement of dopamine enables patients to overcome their previous association of a traumatic even with fear or anxiety because of its role in conditioning 2. Although stimulation of the dopamine reward system generally results in drug addiction, there is not evidence that ecstasy is addictive, especially at low and infrequent doses 8. The involvement of serotonin and dopamine systems account for the positive mental effects associated with ecstasy. Furthermore, because MDMA is also a stimulant (it acts directly on adrenaline receptors) 6, the users who are taking the drug to think about their experiences differently do so in a proactive rather than a lethargic manner.

There are however some negative impacts of ecstasy on the brain. While not addictive (users do not participate in harmful drug-seeking behaviors), MDMA does promote tolerance and withdrawal symptoms 6. In chronic users, higher and higher doses are necessary to achieve the same mental effects. And withdrawal symptoms peak a few days after taking the drug. Because the drug is most often taken over the weekend at parties, the withdrawal period is known as “suicide Tuesdays.” Withdrawal symptoms generally oppose the symptoms of the drug 8, and as such feelings of negative affect are commonplace and physiological symptoms tend not to be severe 6. As mentioned in the forum, it is important to consider how these withdrawal symptoms may affect individuals using drugs in a psychotherapy session differently than those using them as party drugs. However, follow-ups with patients have not led to any concern about this particular issue, as most people say that using the drug was a positive experience. Because they are able to overcome the issues causing them to be anxious or depressed during the ecstasy session, it is possible that the withdrawal period does not pose an additional risk for these patients. Thus, the experience of withdrawal among different types of ecstasy users should be investigated further.

It is not the short-term negative aspects of MDMA that make it a controversial drug, but rather the long-term consequences of ecstasy use. The real debate about the safety of MDMA lies within the topic of neurotoxicity. In the 80s a research team led by Gregory Ricaurte found evidence of neurotoxicity in rats, which led to the emergency classification as a schedule I drug 9. Since that point, the research findings have gone back and forth. For the most part, the only research group to ever find data pointing to extreme toxicity of MDMA has remained to be that led by Ricaurte 10. Other research groups have found modest evidence for structural changes in the brains of humans and animal models exposed to ecstasy. The general finding of the data is that differences between ecstasy-users and non-users, which are highly significant while under the influence of the drug, diminish rapidly as the drug is removed from the system 10. The effects on the brain seem to be temporary and functioning almost entirely returned to baseline after a period of two or three months 10, 11. While there is some evidence that there may be lasting effects on the serotonin system of chronic users 10, there appear to be very few and mild cognitive impacts 12. In a comprehensive study of 34 different cognitive measures, only heavy users, those who had taken the drug more than 50 times, suffered from a decline in nonverbal (visual) memory. All other cognitive functions remained intact 12. Because MDMA used in a therapeutic setting is likely to be used less than five times, the finding of impairment in visual memory is likely to be inconsequential to these patients.

The prevalence of Post-traumatic Stress Disorder in today’s society highlights the need for consideration of ecstasy as a therapy-assisting drug. The two drugs currently approved by the FDA for PTSD are Zoloft and Paxil. Zoloft has been found to only be effective in females, and ineffective in males. While Paxil can work for males and females, both drugs remain largely ineffective for the majority of the population with PTSD 10. Because the currently available drug interventions have proven widely ineffective, it is time to reconsider the ecstasy-mediated therapy sessions of the past. The Multidisciplinary Association for Psychedelic Studies has promoted research on MDMA for the past several years, and is currently funding a clinical trial of MDMA use for PTSD suffers who have previously, and unsuccessfully, tried medication treatment. The study began in 2004 and is currently in the second phase of clinical testing 1. Results thus far are promising 1, 10, and it is possible that completion of the third (and final) phase of clinical trial will be accomplished in the next 4 or 5 years 10. Ecstasy has come a long way, and it’s now possible that the benefits of a different mental outlook in therapy may be offered to PTDS suffers through MDMA.

The class discussion focused largely on the ways in which the government has highly stigmatized the use of MDMA. This has been done through both the classification as a substance I drug and drug abuse prevention propaganda. In light of the potential use of MDMA for PTSD, there was generally a sense of agreement that the government should reconsider this classification and should not prevent research into treatment options. Furthermore, our discussion in class and on the forum highlighted a distinction between MDMA use in therapy and the daily use of SSRIs. MDMA may be preferable to SSRIs because it requires only a few instances of temporarily altering our brains to open up our minds. This is in contrast with the daily use of SSRIs that are meant to continually alter our brain function in order to alter our minds. By temporarily aiding in the processes of thinking differently about trauma, ecstasy ultimately gives the power back to the patient once the substance leaves the body. However, a patient taking SSRIs is always under the influence of the drugs and the mental changes that result. This particular angle of the conversation further highlights an aspect of MDMA treatment that may make it preferable to other medicinal options. The central theme of our discussion was one of support for furthering research on MDMA.

References

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2. A Gift to be Alive: MDMA (‘ecstasy’) in Psychotherapy. From TheDEA.org. Retrieved March 2, 2008, from http://thedea.org/therapy.html

3. Controlled Substances Act. (2008, April 22). In Wikipedia, The Free Encyclopedia. Retrieved March 2, 2008, from http://en.wikipedia.org/w/index.php?title=Controlled_Substances_Act&oldid=207316177

4. Ecstasy (philosophy). (2008, February 1). In Wikipedia, The Free Encyclopedia. Retrieved March 2, 2008, from http://en.wikipedia.org/w/index.php?title=Ecstasy_%28philosophy%29&oldid=188323354

5. Philipkoski, K. (2001) Legal Ecstasy in Five Years? On Wired.com. Retrieved March 2, 2008 from http://www.wired.com/science/discoveries/news/2001/02/41457

6. Effects of MDMA on the human body. (2008, February 29). In Wikipedia, The Free Encyclopedia. Retrieved March 2, 2008, from http://en.wikipedia.org/w/index.php?title=Effects_of_MDMA_on_the_human_body&oldid=194923152

7. Mouse Party- Ecstasy. (2008). Provided by The University of Utah, Genetic Science Learning Center. Retrieved March 2, 2008 from http://learn.genetics.utah.edu/units/addiction/drugs/mouse.cfm

8. Meyer, J.S., and Quenzer. (2005). Psychopharmacology: Drugs, the Brain, and Behavior. Sunderland, Massachusetts: Sinauer Associates, Inc.

9. Doblin, R. (2004). Exaggerating MDMA’s risks to justify a prohibitionist policy. On MAPS.org. Retrieved April 20, 2008, from http://www.maps.org/research/mdmaplan.html

10. Doblin, R. (2002). A clinical plan for MDMA (Ecstasy) in the treatment of Post-traumatic Stress Disorder (PTSD): Partnering with the FDA. On MAPS.org. Retrieved April 20, 2008, from http://www.maps.org/research/mdmaplan.html

11. McCann, U.D., Szabo, Z., Seckin, E., Rosenblatt, P., Mathews, W.B., et al. (2005). Quantitative PET Studies of the Serotonin Transporter in MDMA Users and Controls Using [11C]McN5652 and [11C]DASB. Neuropsychopharmacology. 30: 1741-1750.

12. Madruga, C.B., Boone, K.B., Chang, L., Grob, C., Lee, A., Nations, H., et al. (2003). Neuropsychological Effects of 3,4-Methylenedioxymetnamphetamine (MDMA or Ecstasy) in Recreational Users. The Clinical Neuropsychologist. 17(4):446-459.