Subjective reports of the effects of MDMA in a clinical setting

The paper opens with background on the early clinical use of MDMA in the United States and the regulatory context in California in 1980, where physicians could use non-commercially available drugs within their practice under certain conditions such as peer review and informed consent. Earlier reports of MDMA synthesis and effects are acknowledged, but clinical data were limited. The authors note that this report summarises phenomenological data from the first 29 people given MDMA in a clinical setting, emphasising that the project primarily aimed to assist subjects in achieving personal goals rather than to produce controlled experimental data. This study therefore set out to describe the subjective and therapist-observed effects of single MDMA sessions in a naturalistic clinical context. The investigators explicitly limited their data collection to descriptive accounts before, during and after sessions; no placebo controls, double-blind assessment, independent psychological testing, laboratory organ/metabolic studies or formal physiological monitoring were performed for the whole sample. The report aims to document benefits, undesirable effects, and changes in mood, attitudes, relationships and behaviour that the subjects reported at follow-up.

MDMA for the project was synthesised in Alexander Shulgin's laboratory and its identity confirmed mainly by infrared spectrophotometry; Dr Shulgin assisted during the procedures. Sessions took place between 1980 and 1983 in San Francisco and Santa Fe, New Mexico. All participants (n=29) were self-referred or referred by psychotherapists or friends specifically for MDMA sessions; none were referred from the treating psychiatrist's private practice. A screening questionnaire and a detailed informed consent process (verbal and written) were used; five subjects completed the questionnaire retrospectively at follow-up. Medical exclusion criteria were specified and included hypertension, heart disease, hyperthyroidism, diabetes mellitus, hypoglycaemia, seizure disorder, glaucoma, diminished liver function and pregnancy or possible pregnancy. Individuals with a history of socially or vocationally disabling psychiatric conditions were excluded, with one exception noted where disability was discovered after the session. Prior to sessions, participants agreed to rules intended to create a safe environment (remaining on premises until agreed otherwise; refraining from destructive or sexual activity with therapists; following therapist instructions when part of session structure). Most sessions occurred in subjects' homes. Participants fasted for six hours before dosing to speed absorption and reduce nausea. Oral MDMA doses generally ranged from 75 to 150 mg, adjusted by setting and body weight; a few participants received supplemental doses (typically 50 mg, rarely 75 mg) when effects began to subside. One subject received substantially higher doses (up to 200 mg single dose, 350 mg total) after poor response to lower doses. Individual sessions often used instrumental music and optional eyeshades; interpersonal sessions used background music. Therapists remained attentive and recorded communications. Some subjects received adjunctive medications to manage sympathomimetic or muscular side effects: propranolol (20–40 mg at intervals), single 5 mg diazepam doses, or tryptophan (500 mg) late in sessions. Session duration was typically five to eight hours. Follow-up included immediate verbal contact and later written questionnaires; no systematic laboratory testing or blinded psychological assessments were performed.

Follow-up questionnaires were completed by 28 of the 29 subjects between two months and two years after their last session (most around nine months); one subject replied by letter more than two years later. Presession screening showed 14 of 29 reported psychological problems of mild severity (examples given: dissatisfaction with self, mild depression, anxiety, existential despair); two reported significant medical issues (controlled hypertension in one, chronic macula oedema with ocular implant in another). Benefits during sessions: Every subject reported at least some benefit during their MDMA session. Twenty-seven of 29 felt closer and more intimate with others present; all 21 who had couples or group sessions experienced increased closeness and/or enhanced communication. All 29 reported positive changes in attitudes or feelings: 16 described warmer, euphoric or loving feelings; 10 reported greater self-confidence or self-acceptance; 10 noted lowered defences; five described transcendent experiences; several reported cognitive benefits such as expanded perspective, insight into personal patterns, improved self-examination and creative facilitation (five subjects used low 50 mg doses for creative writing and found it useful). Undesirable effects: All participants reported at least one undesirable experience during or after sessions, generally short-lived (most symptoms resolved within one week). The most common physical complaint was jaw tension, shaking or teeth clenching, reported by 22 subjects; two of these and one other still had it the day after. Diazepam (5 mg) and propranolol (40 mg) relieved jaw tension for some. Twenty-three reported fatigue lasting from hours to a few days (16 for two days or less). Insomnia the night after occurred in 11 subjects; eight experienced muscle aches/tightness; seven felt nausea during sessions, usually brief; two had stomach upset for a day or two. A range of uncommon single-subject physical effects were reported (for example transient visual jitter, lip swelling, fainting). Vital signs recorded in two subjects showed increases in pulse and blood pressure at peak effect (e.g. pulse rising from ~60 to 100–112; blood pressure increases noted). Two subjects experienced longer or more problematic sequelae. Subject No. 14 gained appetite and weight for a few weeks after the session. Subject No. 19 developed weeks-long difficulty coping with work and social relations and had anxiety attacks that caused work absence; he had prior recurrence of similar disabling anxiety episodes. Subject No. 7, aged 74, received substantially higher doses than others and reported numerous acute and subacute physical effects (nausea, vomiting, jaw difficulty, ataxia, blurred vision, urinary urgency, insomnia, transient sensory changes), many of which resolved over days but some of which persisted briefly. Undesirable emotional and cognitive effects were reported by 16 subjects: anxiety or nervousness during sessions (five subjects), mild depression the day after (two subjects), transient confusion or racing thoughts (several subjects), and one report of five to seven days of negative self-talk. Most emotional side effects were brief and self-limited. Realisation of session goals: All but one participant had goals beyond curiosity; 16 felt their purpose was completely realised, four reported significant progress toward all goals, and seven noted partial achievement. Goals varied (cognitive self-understanding, peak/visionary experiences, personal growth, enhanced communication, creative facilitation) with differing rates of fulfilment. For example, among eight seeking peak or mystical experiences, six reported achieving that aim. All five who sought creative-writing facilitation with low doses were satisfied. Changes in psychiatric disorders and psychological outcomes: Of nine subjects carrying DSM-III psychiatric diagnoses, all reported significant improvement; two reported full, lasting remission (subject No. 17, dysthymic disorder, at nine-month follow-up; subject No. 23, postabortion simple sexual phobia). Three with atypical or mixed personality disorders and four other subjects with depressive disorders reported improvement. More broadly, 18 subjects described positive mood changes lasting from hours to several weeks (average about one week), and 23 reported attitudinal changes (average duration roughly one week, some persisting up to two years at follow-up). Reported attitudinal shifts included increased self-esteem (11 subjects), greater acceptance of negative experiences, reduced guilt and increased spiritual orientation among a minority. Interpersonal, occupational and behavioural changes: Two subjects reported negative relationship changes; the remainder reported positive interpersonal outcomes such as improved communication, closeness and conflict resolution. Several couples and individuals maintained improved communication for periods ranging from days to years. Sixteen subjects reported positive occupational changes (less stress, better relationships at work, some income or role changes), though durations varied. Fourteen subjects reported positive changes in spiritual or physical practices (eg, starting or increasing meditation or exercise). Substance use reports (from 28 respondents) showed decreases in use of mood-altering substances in 14 people and increases in three: alcohol decreased in six (two stopped entirely), marijuana use decreased in six (one stopped entirely), caffeine intake fell for five, and tobacco use decreased in two. A few subjects reported increased use of some substances; two frequent cocaine users reported continued abstinence or decreased desire. Fifteen subjects reported changes in life goals, generally toward self-awareness and personal growth. Nine reported altered preferences for experiences sought or avoided, often favouring more openness, intimacy and spiritual orientation. Thirteen reported reductions in attitudes that previously impeded self-actualisation, such as guilt and limiting beliefs.

The authors conclude that, within this small and uncontrolled clinical sample, MDMA appeared physically safe for the 29 participants: no serious adverse physical events were observed and only one subject had a side effect that lasted more than a week. Recorded increases in pulse and blood pressure in two monitored subjects were described as tolerable in healthy people but potentially unsafe for those with vascular disease; accordingly, standard sympathomimetic contraindications apply. Psychologically, most participants reported benefits during and after sessions, including enhanced interpersonal communication, improved mood, increased self-acceptance and reductions in some substance use. All nine participants with DSM-III diagnoses reported significant improvement and two reported lasting remission at follow-up. The investigators suggest that MDMA's most promising therapeutic role may be as an adjunct to facilitate direct communication in close relationships and as a catalyst in insight-oriented psychotherapy. Several subjects explicitly recommended adjunctive use with psychotherapy, and many adopted longer-term practices such as meditation or exercise following their sessions. The authors emphasise caution: MDMA may precipitate a recurrence of previous psychological disabilities in vulnerable individuals, as illustrated by one participant who had disabling post-session anxiety and by another with a prior history of anxiety attacks. They therefore recommend rigorous informed consent about risks, exclusion of people seeking a cure or those with prior disabling psychiatric conditions, and careful screening to select subjects willing to tolerate potentially disturbing experiences. The discussion also notes the reduced apparent reinforcing potential of MDMA described by subjects—namely, diminishing pleasurable effects with repeated or larger doses and increasing adverse effects—which the authors interpret as suggesting limited abuse potential relative to some other drugs. Finally, the authors frame these results as preliminary and descriptive. They state that the presented phenomenological reports should encourage further controlled research into MDMA's therapeutic effects while making clear the limits of its usefulness and discouraging any portrayal of MDMA as a panacea.