MDMAs Role in the Treatment of Depression

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That MDMA is apparently serotonergic was first noted by Nichols and associates (1982), who introduced it in vitro to homogenized rat brains and then measured the release of serotonin from the synaptosomes (vesicles in the synapses that store neurotransmitters). Elevated levels were detected, suggesting that serotonin release may play a role in MDMA's pharmacological activity. Subsequent research described in Peroutka (1990) appears to confirm the drug's serotogenicity. As with serotonergic antidepressant drugs, however, the specific mode of action is uncertain. [See "How MDMA Works in the Brain" for a detailed discussion of what is currently understood of the mechanism of action of MDMA.]

In any case, MDMA's use in psychotherapy to stimulate positive feelings, such as openness and empathy, would seem to recommend it for a possible clinical role in treating depression. Riedlinger (1985) first proposed this in a discussion of MDMA's positive isomer activity and consequent release of serotonin in the brain. Because it is a potent releaser of serotonin into the synapse, and because of its short duration of effect, MDMA seems to be both effective and efficient as a drug for the medical treatment of depression. It works to enhance serotonergic function and mood in a matter of hours instead of weeks (as is the case for most prescription antidepressants), and it is effective when administered infrequendy, perhaps in weekly or monthly dosing intervals. This compares favorably to the multiple daily dosing required for most of the currendy available drugs that can be prescribed for treating depression (such as tricyclic antidepressants, MAO inhibitors, serotonin reuptake inhibitors). The other drugs often take several days or even weeks to produce antidepressant effects and frequendy cause lasting troublesome side effects (appetite and sleep changes, sexual dysfunction, sweating, nausea, and headaches). Compassion for the victims of depression, in addition to the evidence of MDMA's serotonin-releasing effect, should compel further research to establish clearly whether MDMA is indeed an alternative antidepressant.

Treating Suicidal Depression with MDMA

The notion that MDMA might be useful in treating suicidal depression is based on a comparison of psychological patterns in suicidal people and MDMA's psychoactive effects. Psychological characteristics of suicidal people tend to vary between different age groups, cultures, economic classes, and gender (Hendin 1982; American Psychiatric Association 1994). Many cases seem to be manifestations of alienation. The anguish of the suicidal person is frequendy that of a person in exile. He or she feels totally isolated, singled out by fate to suffer hardships and endless frustrations alone. Such people often find it hard to deal with the conflicts and demands of interpersonal relationships. They withdraw into a private, lonely world. Their justification might be that they feel unworthy of love or that others have abandoned them unfairly. In either case, the isolation typically starts to feel irreversible. There seems to be no possibility of ever establishing meaningful contact with other human beings.

According to the Harvard Medical School Mental Health Letter ("Suicide," 1986), "Among the immediate motives for suicide, not surprisingly, despair is most common. In one long-term study, hopelessness alone accounted for most of the association between depression and suicide, and a high level of hopelessness was the strongest signal that a person who had attempted suicide would try again. Intense guilt, psychotic delusions, and even the severity of the depression were much less adequate indicators." The study referred to in the Mental Health Letter, by Beck and colleagues (1985), reported that high ratings on the Beck Hopelessness Scale successfully predicted 90.9 percent of eventual cases of suicide in a sample of 165 hospitalized suicide ideators (people who initially went to the doctor with thoughts of suicide) who were followed for five to ten ygars after taking the test. A subsequent report regarding the study affi^^Sthat "because hopelessness can be reduced fairly rapidly by specific m^pi|tic interventions ... the assessment of hopelessness can potentially improve the prevention as well as the prediction of suicide" (Beck et al. 1989). Hopelessness itself might mediate the relationship between dysfunctional attitudes and psychopathology, especially depression.

Interpersonal attitudes related to depression, not hopelessness per se, also may be the root cause of suicide. To that extent, suicide might be considered an act of interpersonal frustration that seeks to communicate misery and break out of isolation ("Suicide," 1986). This goal may be reached, alternatively and more safely, by means of guided psychotherapy. The recalcitrance of suicidal people, however, is a problem for conventional psychotherapy. For therapy to work, a positive, dynamic interaction must take place between the patient and the therapist (Henry et al. 1990; Talley et al. 1990; Strupp 1993). The patient must be willing to communicate what is going on inside. Someone who is consumed by strong feelings of alienation and hopelessness is likely to resist interpersonal contact and open discussion. Of course, it is frequendy true that patients hesitate to talk about personal problems at the start of psychotherapy and need several sessions before they warm up to the therapist. Time is often a luxury that suicidal patients cannot afford, however. They may be treatable over the long term with conventional psychotherapy, but first they must be stabilized or otherwise prevented from taking their own lives. Usually this means hospitalization, keeping a suicide watch on such patients, and even actively restraining them if necessary.

Here is where MDMA can perhaps play a viable role, based on certain effects and ramifications for guided psychotherapy succincdy described in an issue of the Harvard Medical School Mental Health Letter (Grinspoon and Bakalar 1985): Although MDMA has no officially approved medical or psychiatric application, a few psychiatrists and other therapists had been using it as an aid to psychotherapy for more than fifteen years, in the 1970s and '80s. It has now been taken in a therapeutic setting by hundreds, if not thousands, of people with few reported complications. It is said to fortify the therapeutic alliance by inviting self-disclosure and enhancing trust. Some patients also report changes that last several days to several weeks or longer—improved mood, greater relaxation, heightened self-esteem, and enhanced relations with others. Psychiatrists who have used MDMA with patients suggest that it might be helpful, for example, in marital counseling, in diagnostic interviews, or as a catalyst for insight in psychotherapy. Reports of therapeutic results are so far unpublished and anecdotal and cannot be properly evaluated without more systematic study.

Anecdotal reports by the hundreds of people who have taken MDMA in therapeutic settings are not irrelevant. Their testimonies indicate that certain psychological effects occur consistently across a broad spectrum of usage. This is evident in Adamson's (1985) collection of about fifty such testimonies. The forward, by Ralph Metzner, observes that these firsthand accounts include such words as "ecstasy, empathy, openness, acceptance, forgiveness, and emotional bonding" in reference to MDMA's effects. These are the opposite terms often used to describe the psychological distress of suicidal people: anguish, alienation, recalcitrance, rejection, blame, guilt, and emotional withdrawal. Eisner (1989) also describes several cases of MDMA-assisted psychotherapy in which depression is mentioned specifically as one of the symptoms that is alleviated.

The value of MDMA is that it does not make its users feel better by transporting them into a naive state of bliss. They are aware of the fact that their lives have been burdened by negative thinking, have been based on fears and anxieties. MDMA seems to lend them a different perspective for several hours by minimizing their defensiveness and fear of emotional injury (Greer 1985; Greer and Tolbert 1986, 1990). It stimulates a process by which they are able to look at their problems more objectively and thus transcend a feeling of hopeless entrapment. At the same time, they feel more in touch with their positive emotions. This sustains them as the therapeutic process takes its course. The drug gives them the courage to confront their emotional problems and the strength to work them out, often by enhancing their desire to communicate constructively. Numerous examples of this process are described in Adamson's book (1985).

The particular value of MDMA for suicidal patients and, by extension, for patients with less severe forms of depression is twofold. First, it might be useful as an interventional medicine. By providing the relief from overwhelmingly dark emotions, MDMA likely can help forestall the act of suicide or otherwise alleviate the patient's sense of hopelessness. This buys time for the drug's second major effect, facilitating psychotherapy by helping to enhance the patient's trust and by inviting self-analysis and disclosure. As previously noted, the result is a fortifying of the therapeutic alliance between patient and therapist. Furthermore, MDMA does so in a relatively short time. According to Metzner in Adamson's book (1985): "One therapist has estimated that in five hours of one Adam [MDMA] session clients could activate and process psychic material that would normally require five months of weekly sessions." Needless to say, such accelerated therapeutic healing can mean the difference between life and death for people in imminent danger of suicide.

Risks of MDMA Use

There has been concern about neurotoxicity and other possible health risks from MDMA use. Most of these adverse reactions appear to be avoidable, if samples of known purity are administered in the lowest effective therapeutic dose range and frequency, after carefully screening patients for risk factors. This is consistent with the view of Grob and colleagues (1990) that fears of MDMA neurotoxicity may have been exaggerated and that rigorous clinical trials of the drug in psychotherapy should be resumed. [Most articles that allege neurotoxicity have recruited volunteers with histories of excessive and prolonged use. No study has been published that examines infrequent, single oral dosing.—Ed.]

Animal research with MDMA seems to indicate that even its high-dose neurotoxic effects can be minimized by the concurrent administration of fluoxetine (Schmidt 1987; Schmidt et al. 1987). One report by McCann and Ricaurte (1993) suggested that fluoxetine pretreatment, at doses of 20 to 40 mg, does not compromise MDMAjs therapeutic effects and, furthermore, decreases post-session insomnia and fatigue. A cautionary editorial by Price and colleagues (1990) maintains that it is premature to pursue clinical trials of MDMA in conditions that are not hfe-threatening. Both sides would be served by exploring the possible use of MDMA as an intervention drug for the stabilization and subsequent treatment of patients afflicted with severe and perhaps suicidal depression.

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