DPT as an adjunct in psychotherapy of alcoholics

Earlier clinical work in Canada and the United States suggested that psychedelic-assisted psychotherapy with LSD could produce clinically meaningful improvements in alcoholism when used as an adjunct to psychotherapy rather than as a mere pharmacological intervention. Those controlled studies reported improvements on a range of psychological measures and on follow-up evaluations, but investigators also noted drawbacks of LSD for therapeutic use, notably its long duration and prolonged, fluctuating termination period of altered consciousness. Grof' and colleagues therefore sought an alternative compound with LSD-like therapeutic qualities but a shorter and more abrupt action. They identified alkylated tryptamine derivatives as candidates and, based on prior reports that dipropyltryptamine (DPT) produced phenomenology comparable to LSD with a briefer time-course, initiated an exploratory clinical study to evaluate DPT as an adjunct to psychotherapy for alcoholic patients. The study aimed to gain clinical experience with DPT, assess its safety, and obtain preliminary indications of therapeutic usefulness in this population.

This was an exploratory, open clinical study conducted on 51 alcoholic patients drawn from the Alcoholic Rehabilitation Unit of Spring Grove State Hospital. Patients were selected on the basis of medical and psychiatric screening to determine suitability for psychedelic-peak therapy; exclusions included organic brain damage, epilepsy, active renal or hepatic disease, severe cardiovascular disorders and overt psychosis. Patients were not excluded for severity of drinking or poor prognosis. Demographic details reported: ages 27–60 (mean 38.6), a mix of marital statuses, 42 Caucasian, 8 Black and 1 of mixed ancestry, average duration of alcohol problems 10.4 years, and an average of 1.9 prior state hospital admissions. The therapeutic procedure followed a three-phase model used in prior psychedelic studies: preparatory drug-free interviews (typically 12–15 hours over 2–3 weeks), one or more DPT-assisted sessions, and several post-session integration interviews. DPT was administered intramuscularly as an aqueous solution (15 mg per cm3); high doses of 60–150 mg IM were used for the study sample. Sessions took place in a comfortable suite with a therapist and a psychiatric nurse in attendance; patients often wore eyeshades and listened to stereophonic classical music during sessions. The number of DPT administrations ranged 1–6 (mean 1.86). The average total therapy time (preparation plus sessions) was 36.4 hours, and time in treatment ranged 2–22 weeks (mean 8 weeks). After discharge, no routine psychotherapy was provided; an independent follow-up team of social workers performed follow-up assessments. Outcome assessment combined multiple methods. A pretreatment battery (re-administered 3–5 days after treatment) included the Minnesota Multiphasic Personality Inventory (MMPI), Personal Orientation Inventory (POI), Raven Progressive Matrices, Psychiatric Evaluation Profile (PEP) and Benton Visual Retention Test. Social functioning over the two years before hospitalisation and at follow-up was quantified using a precoded social history questionnaire with six 10-point scales (interpersonal, occupational, residential, global adjustment, alcohol consumption/abstinence and interference by drinking). Session effects were assessed via therapist observations, patient written accounts and a psychedelic experience questionnaire. Two pre- and two post-session blood samples were taken for chromosomal analysis; preliminary processing was reported. The extracted text truncates the description of the data-analysis methods: it notes that data were tabulated and punched on IBM cards but does not fully report the statistical procedures used.

Clinical observations indicated that DPT produced rapid-onset psychedelic effects after parenteral administration; oral dosing was ineffective. The threshold for psychological effects was about 10–15 mg IM; the study used high doses (60–150 mg) for the 51 patients. Onset typically occurred within 5–20 minutes. Low-dose sessions lasted about 1.5–2 hours, while high-dose sessions lasted about 4–6 hours; termination of DPT sessions was described as relatively abrupt and lacked the prolonged oscillations seen with LSD. Phenomenology ranged from aesthetic experiences and reliving of emotionally relevant memories with abreaction to profound mystical or peak experiences similar to those observed with LSD. Psychometric comparisons between pre- and immediate posttreatment testing showed statistically significant improvements on multiple measures. MMPI composite profiles (48 patients with complete data) showed highly significant reductions (p < 0.001) on Depression (D), Welsh's first factor (A), Psychasthenia (Pt), Social Introversion (Si) and the F scale; the K scale also showed a significant increment. POI profiles (48 patients) improved across all scales, with all increments significant at p < 0.001; the largest changes were in self-regard (Sr), time competence (Te), inner-directedness (I), the support ratio (0-1), self-actualising values (SAV) and spontaneity (S). Raven Progressive Matrices (47 patients) showed a mean IQ increase of 4.39 points (p < 0.001). PEP results (36 patients) demonstrated significant improvement in insight (p < 0.001), distress (p < 0.001) and the SD scale (p < 0.01). The Benton Visual Retention Test (44 patients) did not show significant pre-to-post differences. Follow-up data at six months were available for 47 of the 51 patients (92.1%). Ratings on the social history questionnaire indicated statistically significant improvements across occupational, residential, interpersonal and global adjustment and abstinence; changes in interpersonal adjustment, abstinence and global adjustment reached p < 0.001. Using an a priori criterion of scores >8 on the 10-point scales for global adjustment and drinking behaviour to indicate ‘essential rehabilitation,’ 22 patients (46.8%) met that threshold for global adjustment and 25 patients (53.2%) for abstinence. A total of 18 patients (38.2%) remained completely abstinent during the entire 6-month follow-up period. Chromosomal analyses were being processed and preliminary findings did not suggest chromosomal damage in white blood cells. Safety signals included one patient who developed a brief psychotic episode three weeks after the last DPT administration; the episode required readmission and responded to conventional antipsychotic treatment (Mellaril). The investigators noted that this patient had pre-existing severe neurotic symptoms and had been exposed to additional stressors (prolonged fasting, sleep deprivation and dehydration) that may have contributed.

Grof' and colleagues interpret the findings as indicating that DPT can be used as an adjunct to brief intensive psychotherapy in alcoholic patients with effects comparable to those they and others have reported for LSD-assisted psychotherapy. They emphasise that DPT was generally well tolerated biologically and psychiatrically in this series, noting the single brief psychotic episode and describing its clinical context and likely contributing factors. Preliminary chromosomal data did not suggest genotoxic effects, according to the authors. The investigators compare the degree of clinical improvement and 6-month follow-up outcomes with those observed in a prior high-dose LSD study and find them broadly similar; however, they caution that direct comparison is limited because the studies were not contemporaneous, patients were not randomly assigned between treatments, and different therapists and treatment circumstances applied. They also note pharmacological differences: DPT has a shorter duration and more abrupt termination than LSD, though on average more DPT sessions were given. Key limitations acknowledged by the authors are that this was a pilot, uncontrolled study without a concomitant control group, so causal inferences are limited and direct comparisons with LSD require a properly controlled trial. The authors state that the main value of the study was clinical experience with DPT and preliminary indications of safety and usefulness, and they indicate that a specially designed controlled study is now in progress.