This open-label longitudinal study (n=59) investigated the efficacy of a single versus three sessions of ketamine-assisted psychotherapy (140mg/70kg/session) for people with heroin dependence and found that the three-session program is more than twice as effective (abstinence 50% vs. 22.2%) one year after treatment.
Papers cited by this study that are also in Blossom
Krupitsky, E. M., Burakov, A. M., Romanova, T. N. et al. · Journal of Substance Abuse Treatment (2002)
Introduction
A prior study found that one ketamine-assisted psychotherapy session was significantly more effective than active placebo in promoting abstinence (Krupitsky et al. 2002).
Methods
In this study of the efficacy of single versus repeated sessions of ketamine-assisted psychotherapy in promoting abstinence in people with heroin dependence, 59 detoxified in patients with heroin dependence received a ketamine assisted psychotherapy (KPT) session prior to their discharge from an addiction treatment hospital, and were then randomized into two treatment groups. Participants in the first group received two addiction counseling sessions followed by two KPT sessions, with sessions scheduled on a monthly interval (multiple KPT group). Participants in the second group received two addiction counseling sessions on a monthly interval, but no additional ketamine therapy sessions (single KPT group).
Results
At one-year follow-up, survival analysis demonstrated a significantly higher rate of abstinence in the multiple KPT group. Thirteen out of 26 subjects (50%) in the multiple KPT group remained abstinent. compared to 6 out of 27 subjects (22.2%) in the single KPT group (p < 0.05). No differences between groups were found in depression, anxiety, craving for heroin, or their understanding of the meaning of their lives.
Discussion
It was concluded that three sessions of ketamine-assisted psychotherapy are more effective than a single session for the treatment of heroin addiction.
Earlier research on psychedelic-assisted psychotherapy suggested that a single high-dose session can produce pronounced short-term therapeutic effects that often attenuate after a few weeks, a phenomenon described as the ‘‘psychedelic afterglow’’. Ketamine, an NMDA receptor antagonist used at sub‑anaesthetic doses, produces intense, sometimes transformative experiences that share features with near‑death phenomena and have been reported to prompt insights, shifts in life meaning and motivation that may support abstinence from substances. Prior single‑session ketamine‑psychotherapy (KPT) studies in people with alcohol and heroin dependence indicated clinical benefit, but did not address whether repeating sessions could extend or stabilise those benefits. Krupitsky and colleagues set out to compare the efficacy of a single KPT session versus a multiple‑session KPT regime (three sessions total, spaced one month apart) for promoting abstinence in people with heroin dependence. The study aimed to test whether administering additional monthly KPT sessions, with preparatory and integration counselling, would increase one‑year abstinence rates relative to a single inpatient KPT session followed by counselling only.
This was a randomised clinical study conducted after inpatient detoxification. Fifty‑nine heroin‑dependent inpatients who met the inclusion and exclusion criteria were enrolled and all received an initial KPT session while still hospitalised. Randomisation into treatment arms occurred after that first KPT session but before any subsequent sessions or counselling. Participants were then allocated to either a multiple KPT group (two additional monthly KPT sessions plus counselling) or a single KPT group (no further KPT, only counselling at monthly intervals). Key procedural elements included intramuscular ketamine at 2.0 mg/kg administered during each KPT session, a psychotherapeutic setting with eye shades and music, and existentially oriented psychotherapy focused on meaning and motivation for sobriety. Before the first ketamine session participants received five hours of preparatory psychotherapy and five hours of post‑session integration psychotherapy; before the second and third KPT sessions the multiple‑KPT group received one hour of counselling to prepare and one hour thereafter to integrate the experience. An anaesthesiologist was present for all KPT sessions. Clinical evaluators who performed psychological and clinical assessments during treatment and follow‑up were blind to group assignment. Eligibility criteria required current heroin dependence for at least one year, age 18–35, at least high school education, at least two weeks' abstinence from heroin and other substances, no psychotropic medication, and the availability of a relative to assist with follow‑up, among other practical requirements. Exclusion criteria included major psychiatric disorders (organic, schizophrenia, major affective disorder), seizure disorder, alcoholism or polydrug dependency, significant medical disease, pregnancy, and other conditions that would contraindicate participation. Outcomes and follow‑up procedures were structured around abstinence as the primary outcome, determined by monthly follow‑up interviews, physical examination for injection marks, urine toxicology and collateral reports from relatives over 12 months. Secondary outcomes comprised psychometric measures administered before and after sessions and at follow‑up: Zung Self‑Rated Depression Scale (ZDS), Spielberger State‑Trait Anxiety Scale (SAS), a Visual Analog Scale of Craving for Heroin (VASC), and the Purpose‑in‑Life Test (PLT). Statistical analysis used SPSS 11.0; survival analysis (Kaplan‑Meier) assessed differences in abstinence over time, and repeated‑measures MANOVA with post‑hoc Tukey tests analysed psychometric changes.
treatment for alcoholism and addictions). However, it is difficult to generalize across these studies because of differences in methodology. After they were scheduled in 1970, the use of psychedelic drugs in research was strictly limited, significantly curtai ling Krupitsky et at. the development of studies employing more sophisticated methods. However, data collected in the 1950s and 1960s provide some important insights about treatment effects of psychedelic psychotherapy, which have been summarized incomprehensive review. One of the insights gained from previous research concerns the transient psychotherapeutic and psychologi cal effects of psychedelic psychotherapy. The effects of psychedelic psychotherapy are often very pronounced within several days or weeks after a treatment session, but then these effects quickly decline. This phenomenon was termed a "psychedelic afterglow. "described an afterglow as a positive post-hallucinogen state occurring in subjects after they have a transcendent psychedelic peak experience: If a psychedelic-peak experience has been achieved and sta bilized during the session, a clinical picture which we have termed the psychedelic afterglow can be observed in the days after the session. Mood is elevated and energetic; there is a relative freedom from concerns of the past and from guilt and anxiety, and the disposition and capacity to enter into close interpersonal relationships is enhanced. These psychedelic feelings generally persist for from two weeks to a month and then gradually fade into vivid memories that hopefully will still influence attitude and behavior. During this immediate postdrug period, there is a unique opportunity for effective psychotherapeutic work on strained family or other interper sonal relationships. Ketamine is a drug used for anesthesia that acts as an NMDA receptor antagonist. Sub-anesthetic doses produce profound transformative experiences that share many ele ments with some near-death experiences. Previous studies have found that this experience often causes important insights about the self and the world, and can help people accept a new meaning of life, new values and new purpose in life related to abstinence from drugs and alcohol. Recent studies that employed a single-session ketamine psychotherapy (KPT) paradigm for alcohol and heroin-de pendent patients have demonstrated that KPT is an effective treatment in promoting abstinence in alcoholicsand heroin addicts. However, these studies did not clarify whether the effect of a single KPT session might be further enhanced by repeated sessions. The major aim of this study was to compare the efficacy of a single session of ketamine-assisted psychotherapy with a multiple (three session) KPT regime in people with heroin dependence. The authors sought to determine whether the repeated sessions of KPT carried out over one-month inter vals would improve the efficacy of a single KPT session, as reflected in objective measures of treatment outcome, such as abstinence from heroin on follow-up. In other words, could the efficacy of KPT in treating heroin dependence be Ketamine Psychotherapy for Heroin Dependence increased by administering multiple KPT sessions and thus stabilizing the afterglow?
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Papers in Blossom that reference this study
Gent, E. M., Bryan, J. W., Cleary, M. A. et al. · Journal of Psychopharmacology (2024)
Thal, S. B., Wieberneit, M., Sharbanee, J. M. et al. · Journal of Humanistic Psychology (2023)
Hull, T. D., Malgaroli, M., Gazzaley, A. et al. · Journal of Affective Disorders (2022)
Soares, C. M., Leite, A., Pinto, M. · Journal of Psychoactive Drugs (2022)
Nigam, K. B., Pandurangi, A. K. · SN Comprehensive Clinical Medicine (2021)
Palhano-Fontes, F., Gorman, I., Nielson, E. M. et al. · Frontiers in Psychology (2021)
Rothberg, R. L., Azhari, N., Haug, N. A. et al. · Journal of Psychopharmacology (2020)
Krediet, E., Bostoen, T., Breeksema, J. J. et al. · International Journal of Neuropsychopharmacology (2020)
Ezquerra-Romano, I. I., Lawn, W., Krupitsky, E. M. et al. · Neuropharmacology (2018)
Jones, J. L., Mateus, C. F., Malcolm, R. J. et al. · Frontiers in Psychiatry (2018)
Schenberg, E. E. · Frontiers in Pharmacology (2018)
Noorani, T., Garcia-Romeu, A., Swift, T. C. et al. · Journal of Psychopharmacology (2018)
Dos Santos, R. G., Bouso, J. C., Hallak, J. E. · Journal of Psychedelic Studies (2016)
Bogenschutz, M. P., Forcehimes, A. A. · Journal of Humanistic Psychology (2016)
Liu, Y., Lin, D., Wu, B. et al. · Brain Research Bulletin (2016)
Of 73 patients screened, 59 met entry criteria (mean age 22.6 ± 3.9 years; mean heroin use duration 38.8 ± 30.4 months; 49 males, 10 females) and received the initial KPT session. Six participants relapsed and dropped out within the first month after that initial session, before randomisation. The remaining 53 participants were randomised: 26 to the multiple KPT group and 27 to the single KPT group. Baseline characteristics (age, duration of heroin use, gender) did not differ significantly between groups. During the treatment phase, four of 26 participants in the multiple KPT group (15.4%) relapsed after the second session but before the third, while seven of 27 in the single KPT group (25.9%) relapsed after the first counselling session; the difference in retention during treatment was not statistically significant. Kaplan‑Meier survival analysis over the 12‑month follow‑up showed a significantly higher abstinence rate in the multiple KPT group throughout the year. At one year, 13 of 26 participants (50%) in the multiple KPT group remained abstinent compared with 6 of 27 participants (22.2%) in the single KPT group (p < 0.05). The authors also note that if the six participants who relapsed prior to randomisation are counted with the single‑KPT cohort, the single‑session abstinence rate at 12 months would fall to 18.2%. On psychometric secondary outcomes, depression, state and trait anxiety, and heroin craving were significantly reduced after the first KPT session in both groups and continued to decrease in participants who remained in follow‑up; there were no significant differences between single and multiple KPT groups on ZDS, SAS, VASC or PLT scores. Purpose‑in‑Life (PLT) scores improved similarly in both groups. Safety findings reported no cases of protracted psychosis, flashbacks, or ketamine addiction; the only noted adverse effect was an acute increase in blood pressure (particularly diastolic) of about 20%–30% during KPT sessions.
Krupitsky and colleagues interpret their findings as evidence that a program of three KPT sessions spaced monthly is more effective at promoting one‑year abstinence from heroin than a single KPT session followed by counselling. The multiple‑session group had an abstinence rate more than twice that of the single‑session group at 12 months (50% versus 22.2%), and Kaplan‑Meier analysis indicated this advantage persisted across the year. The authors relate these results to historical observations with other psychedelic therapies in which single‑dose benefits tended to fade, proposing that repeated sessions may stabilise the ‘‘psychedelic afterglow’’ and thereby prolong therapeutic gains. The authors acknowledge key limitations. No placebo or non‑ketamine control arm was included in this trial, so effects attributable to ketamine per se cannot be disentangled from those of psychotherapy or nonspecific factors in this dataset; however, they cite a prior study in which high‑dose ketamine outperformed an active placebo. Randomisation occurred after the initial KPT session and six early relapses prior to allocation could influence comparability; the authors note that including those six with the single‑session cohort would lower the single‑session abstinence rate further. Another limitation is that psychometric measures used in the study did not detect differences between groups, suggesting that the mechanism by which multiple sessions improve abstinence may involve shifts in attitudes or life‑meaning (the afterglow) that were not captured by the instruments employed. In terms of clinical implications, the investigators suggest that multiple KPT sessions merit further study as a promising approach for heroin dependence, and they note that the multiple‑session abstinence rate compares favourably with published outcomes for oral naltrexone in similar contexts. They recommend future research to include control conditions and measures better able to quantify the putative afterglow or changes in life‑view, and they emphasise ongoing attention to safety monitoring given the acute cardiovascular effects observed during sessions.
After detoxification, 59 heroin-dependent participants were assigned to one of two groups on a random selection ba sis. The randomization was done after the first KPT session, but prior to the second session of KPT or counseling. The participants in the multiple KPT group received three KPT sessions with a psychedelic (hallucinogenic) dose of ketamine (2.0 mglkg i.m.), with one-month intervals between sessions. They received their first KPT session as inpatients after detoxification, just before being discharged from a psychiatric hospital. They came to the same hospi tal one and two months later for the second and third KPT sessions as outpatients. An individual addiction counseling session was conducted every time before the repeated (sec ond and third) KPT sessions. The participants in the single KPT group received only one KPT session with the same dose of ketamine and the same psychotherapeutic technique and environment as participants in the multiple KPT group. They received the KPT session as inpatients after detoxification, prior to being discharged from the psychiatric hospital . After one and two months, the same psychotherapist who carried out the KPT conducted an individual addiction counseling session at the psychiatric hospital. All participants were treated alike and were given the same preparation for KPT. The KPT sessions, regardless of their number, were given under uniform circumstances at the same psychiatric hospital. Clinical evaluators blind to whether participants had received one or three KPT ses sions performed psychological and clinical evaluations on all participants during treatment and fol low-up periods.
Out of 73 heroin-dependent patients screened, 59 of them (mean age M ± SD = 22.6 ± 3.9 years, duration of heroin abuse 38.8± 30.4 months, 49 males and 10 females) met inclusion criteria and were included in the study. Par ticipants were recruited from the inpatient department of the Leningrad Regional Center of Addictions, a 300-bed hospital for treating patients with alcoholism and chemi cal dependencies who are living in the Leningrad Region. Informed consent was obtained from all participants prior to acceptance into the study. The study was approved by the Human Experimentation Ethical Committee at St. Petersburg Pavlov State Medical University.
A psychotherapist specially trained by the investiga tor in conducting KPT provided psychotherapy to study
The fol lowing exclusion and inclusion criteria were employed for participant selection: • I ncl usi on criteria: I CD-10/DS M -IV criteria of current heroin dependence present for at least one year; age between 18 and 35; at least high school education; abstinence from heroin and other substances of abuse for at least two weeks; not currently on psychotropic medication; at least one relative willing to assist in fol low-up and provide outcome data; stable address within St. Petersburg or nearest district of Leningrad Region; participant has a home telephone number at which he/she can be reached; not currently on proba tion; and competency to give informed consent and otherwise participate. • Exclusion criteria: ICD-10/DSM-IV criteria of organic mental disorder, schizophrenic disorder, paranoid disorder, major affective disorder, or seizure disorder; ICD-10/DSM-IV criteria for alcoholism or polydrug dependency; advanced neurological, cardiovascular, renal, or hepatic diseases; pregnancy; family history of psychiatric disorders listed above; clinically signifi cant cognitive impairment; active tuberculosis or current fe brile illness; AIDS; significant laboratory abnormal ity such as severe anemia, unstable diabetes, or liver function tests more than three times above normal ; pending legal charges with potential impending incar ceration; concurrent participation in another treatment study; or concurrent treatment in another substance abuse program.
The participant's evaluation included a formal psychi atric and clinical examination and a battery of psychiatric and psychological scales. Formal psychiatric and clinical examination included a standard medical examination, with blood chemistry panel (including hepatic functions), urine analysis, pregnancy test, electrocardiogram, and review of previous medical and psychiatric records. The psychological assessment consisted of two parts, psychiatric assessments and psychological assessments. Psychiatric symptoms were assessed with Zung Self-Rated Depression Scale (ZDS; Zung 1965), Spielberger Self-Rated State-Trait Anxiety Scale (SAS;), and the Visual Analog Scale of Craving for Heroin (VASC;. Psychological assessment consisted of the Purpose-in-Life Test (PLT; Crumbaugh 1968) based onconcept of people's aspiration for the mean ing of life, intended to assess the participant's understanding of the meaning of his/her life. All international rating scales Ketamine Psychotherapy for Heroin Dependence mentioned above had been specially adapted and validated in Russia before the study.
During the treatment phase, the investigators performed urine drug testing before the fi rst KPT session in both groups, before each successive KPT and counseling session in the multiple KPT group, and before each addiction counseling session in the single KPT group. The ZDS, SAS, VA SC, and PLT were administered before and after the first KPT session in both groups, before and after the second and third KPT and addiction counseling sessions in the multiple KPT group, and before and after each of the two addiction counseling sessions in the single KPT group. One month after the final treatment, and then at three month intervals for the remainder of the year, participants completed a follow-up interview in person with a research assistant. Each participant underwent a physical examina tion to determine the presence or absence of traces (marks) of injections on his or her veins, and a urine sample was collected for drug testing. Information from the physical examination was used to determine whether a participant had abstained from heroin. Abstinent participants completed the ZDS, SAS, VA SC, and PLT during this examination. In addition, psychiatrists blind to condition collected fol low-up data on a monthly basis for up to 12 months after the end of the treatment phase (the last session). During monthly telephone interviews, the psychiatrists collected self-reported information from the participant about his/her drug use during the follow-up period, using the Time Line Follow Back technique. Information from the participant's relatives about the participant's drug use was collected in the same manner.
Before the fi rst ketamine session, participants received five hours of psychotherapy focused on the participants' addictions to prepare them for the ketamine session, and they received five hours of psychotherapy after the first ketamine session to help them to interpret their experience during the ketamine session and integrate it into everyday life. One hour of addiction counseling was provided before the second and third KPT sessions to prepare participants to explore issues related to their chemical dependence during those sessions. After the second and third KPT ses sions, participants in the multiple KPT group received an additional hour of psychotherapy after each session to help them integrate their experience during these sessions. An anesthesiologist was available throughout all ket amine sessions to treat any possible complications. Ketamine was injected intramuscularly at the dose of 2 mglkg. The length of a ketamine session was between 1.5 and two hours. The participant was instructed to recline on a couch with eye shades. The participant listened to a preselected program of music throughout the session. The psychotherapist provided
emotional support for the participant and carried out psycho therapy during the ketamine session. The psychotherapy was existentially-oriented, focusing on assisting the participant to consider and formulate a purposeful or meaningful life, but also took into account the participant's individual ity, and his or her specific personality problems. This therapy aimed to establish a strong personal motivation for a sober life without drugs. The ketamine experience is similar to some near-death experiences (Jansen 200 1), and it may produce a positive shift in the participant's understanding of the meaning of life, life purposes, and spiritual development through mechanisms similar to those seen with near-death experi ences The major goal of the psychotherapy provided before, dur ing, and after KPf sessions was to assist the participant in reaching this positive shift The details of KPf technique and psychotherapeutic intervention have been described in previous publications. Ketamine produces diverse experiences ranging from spiritual rapture to fear and even horror, sometimes all in the same person and during the same session. People have reported experiencing violent or rapid travel through tunnels or corridors, derealization, extreme depersonalization asso ciated with intense fear or euphoria, and feeling connected to God or a higher power. The transformative experiences often began with extreme fear, including fear of the world ending or apocalypse, and often ended in an experience of rebirth associated with oceanic, or positively experienced, ego loss and boundlessness. All of these experiences were emotionally intense and compelling. Many people reported great difficulty in expressing their experiences in words. It should be noted that despite these common themes, the pa tient almost always experienced individually specific themes that reflected the individual 's case history and personality problems in symbolic form. After the first KPf session, all participants received an addiction counseling session at their second and third monthly scheduled appointments. These sessions included manualized addiction counseling procedures used in Rus sia, which include elements of cognitive-behavioral therapy and a motivational enhancement approach. Participants in the multiple KPf group also received brief instructions preparing them for additional KPf during these addiction counseling sessions.
Data management and analysis were performed with SPSS 11.0 statistical software package. The rate of absti nence was considered the primary outcome variable. The psychometric data were treated as secondary outcome variables, with each scale considered independent of other scores. Survival analysis (Kaplan-Meier survival function) was employed to assess differences in the rate of abstinence between the single and multiple KPf groups. MAN OVA within-subjects repeated measures of analy sis design with Tukey test for post-hoc comparisons were employed to assess the effect of single versus repeated KVf and counseling sessions and changes in psychometrics over the treatment and follow-up periods. Independent variables were participant's condition (single or multiple KVf) and fo llow-up time point, and dependent variables were ZDA, SAS, VA SC, and PLT scores.
Six out of 59 participants enrolled in the study (mean age M ± SD = 23.0 ± 5.5 years, duration of heroin abuse 48.3 ± 48.0 months, five males and one female) relapsed and dropped out of treatment within the first month after the initial KVf session. Prior to the second session, the 53 re maining participants were randomized into the two treatment groups. Twenty-six participants (mean age M ± SD = 22.4 ± 4. 1 years, duration of heroin abuse 36.5 ± 27.6 months, 21 males and five females) were assigned to the multiple KVf group and received two more KVf sessions, includ ing addiction counseling sessions before KVf, separated by one-month intervals. Twenty-seven participants (mean age M ± SD = 22.7 ± 3.5 years, duration of heroin abuse 38.9 ± 29.2 months, 23 males and four females) were assigned to the single KVf group and received two addiction counseling sessions separated by one-month intervals. There were no statistically significant differences between these groups in the mean age, duration of heroin addiction, and gender. In the multiple KVf group, four out of 26 participants (15.4%) relapsed and dropped out of treatment after the second KVf session but prior to the third. In the single KVf group, seven out of 27 participants (25.9%) relapsed and dropped out of treatment after the first counseling session. The difference in the retention in treatment phase between the two groups was not statistically significant. However, Kaplan-Meier survival analysis revealed sta tistically-significant differences in the follow-up abstinence rate between groups: the abstinence rate was significantly greater in the multiple KVf group throughout the year of the follow-up (Figure). At the end of the one-year follow-up, 13 out of 26 participants (50%) in the multiple KVf group remained abstinent compared to six out of 27 participants (22.2%) in the single KVf group (p < 0.05).
Symptom intensity for all measures administered (depression, state and trait anxiety, and craving for heroin) were significantly reduced after the first KVf session in both groups, and then gradually decreased further in both groups in those participants who did not relapse and who showed up for scheduled appointments. There were no significant di ff erences in these scores between the single and multiple KPT groups (see Table). Those who relapsed were Ketamine Psychotherapy fo r Heroin Dependence unavailable for psychometric evaluation. The understand ing of the meaning of life measured by the PLT improved in both groups in a similar manner (Table), and there were no statistical differences between the two groups.
There were no complications, such as protracted psy chosis or flashbacks, after KVf. No participant taking part in the study became addicted to ketamine. The only side effect noted in all participants was an acute increase in systolic and particularly diastolic blood pressure of 20% to 30% during the ketamine psychotherapy session.
Results of this study showed that a three session KVf program is more effective in promoting abstinence from heroin addiction than a single KVf session followed by two counseling sessions. The rate of abstinence was signifi cantly higher in the three KVf session group throughout a year of fol low-up. At the end of one year, the rate of abstinence in the multiple KVf sessions group (50%) was more than twice as high as in the single KVf session group (22.2%). Furthermore, if we include the six participants who relapsed after a single KVf session but prior to condition assignment into the single KVf group, it lowers the rate of abstinence at 12 months to 18.2%, lending further support to the conten tion that a single KVf session does not provide the same benefits as multiple KVf sessions. These results correspond very well with the observations made in clinical studies with psychedelics carried out in the 1950s and 1960s that provided the rationale for the multiple session approach used in this study. In particular,noted that, "the longer fol low-up, the less improvement was observed across the single dose studies." In the review of, the authors wrote that "Some controlled studies show an improvement lasting from several weeks to several months ... The obvious recourse of supplemen tary treatments every once in a while has been suggested but never taken seriously possibly because everyone is mesmerized by the vision of a quasi-miraculous single shot cure ... " This study does not compare ketamine-assisted therapy with placebo, raising issues of separating effects resulting from ketamine-assisted therapy versus those arising from psychotherapy or from placebo effect. However, a prev i ous investigation we conducted has addressed this issue, finding that high-dose ketamine produced a greater rate of abstinence from heroin than psychotherapy conducted with active placebo. Building on these findings, we chose to examine whether multiple (three) psychotherapy sessions could produce greater benefits than a single session. It is interesting to note that the 22.2% rate of abstinence after one year in the single KVf session group in this study was similar to the one year abstinence rate of 24% after a single KPf session in a previous study of KPT for heroin addiction, in which a single KPf session was compared to a single active placebo session (a low, nonpsychedelic dose of ketamine). Due to the close similarities in rate of one year abstinence in the single KPf groups in this current study and in the previous study, it seems likely that the groups are well-matched. This supports the assumption that, were a placebo group to have been added to this current study, the rate of one year abstinence would have been somewhat similar to that in the earlier study, or 6%. It is also notable that the rate of abstinence for single KPf participants was similar to the rate of reten tion in treatment for people receiving the opioid antagonist naltrexone, and the rate of abstinence in the multiple KPf was even higher than after naltrexone treatment. These findings suggest that multiple sessions of Ketamine Psychotherapy fo r Heroin Dependence KPT hold promise as a treatment for people with heroin dependence, and that multiple sessions are better than a single session of KPT, despite lack of significant differences between the two groups in self-reported depression, anxiety or cravings for heroin. The lack of significant differences between single and multiple KPf groups on other outcome measures, includ ing those for depression, anxiety, life purpose and heroin craving, suggests that increased rates of abstinence in the multiple KPf group is at least partly due to factors not mea sured in this study. This effect could be related to a specific shift in the participant's mind and his or her attitude to life that was described byas an "afterglow," and for which we do not yet have a rating scale to measure. In the future, we may employ measures more li able to capture this shift or change in attitude or life view.
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