Ketamine-Assisted Psychotherapy (KPT) of Heroin Addiction: Immediate Effects and Six Months Follow-Up Evgeny M. Krupitsky, M.D., Ph.D. Andrey M. Burakov, M.D., Ph.D. Tatyana N. Romanov, Ph.D. Alexander Y. Grinenko, M.D., Ph.D. Rick J. Strassman, M.D. In the 20th century, while billions of dollars have these substances had essentially come to an end in been spent to treat addictive diseases, the search for America because of controversy associated with their effective medication continues. The mainstay of such non-medical use (Halpern, 1996). treatments includes therapy and counseling, AA and Later in the 1980's and 1990's both animal studies NA, different kinds of rehabilitation programs, drug and anecdotal human reports suggested anti-craving maintenance programs, and pharmacotherapy. The ef- properties of another hallucinogen--ibogaine ficacy of all these suggested methods of addiction treat- ("Endabuse") (Lotsof, 1995; Mash, 1998). However, ment is not enough, however, and still there is a need further human research with ibogaine is needed to dem- for new effective medications. The use of hallucino- onstrate its antiaddictive properties as well as safety. gens in the treatment of addictions could be one prom- Ketamine is a drug for general anesthesia, but in ising approach (Halpern, 1996). subanesthetic doses it induces a profound psychedelic Many addiction studies in the 1950's and 1960's (hallucinogenic) experience (Bowdle et al., 1998). (Grinspoon and Bakalar, 1979), suggested that hallu- Ketamine has several advantages over other halluci- cinogen-assisted (psychedelic) psychotherapy might be nogens as an adjunct to psychotherapy in the treat- an efficient treatment, but different methodologies ment of addictions: it is safe, short-acting, and, most made it difficult to generalize across studies. importantly, it is not a scheduled drug like other hallu- In the 1970's Savage and McCabe (1973) showed cinogens. Our previous studies showed that ketamine- that LSD-assisted psychotherapy had a positive effect assisted psychotherapy is an effective method for al- on the outcome of treatment of heroin addicts: 25% of coholism treatment (Krupitsky and Grinenko, 1997). the subjects treated with LSD remained abstinent from Also, ketamine could have anti-craving properties opiates for one year as opposed to only 5% of the con- because of its influence on the NMDA receptor, simi- trol group of conventional weekly group psycho- lar to other NMDA receptor ligands-acamprosate and therapy. ibogaine (Mash et al., 1998; Sass et al., 1996). All these The authors encouraged further research with hal- factors led us to study the efficacy of ketamine-assisted lucinogens in the treatment of addictions, but by 1973, psychotherapy for heroin dependence. when their study was published, human research with St. Petersburg Scientific-Research Center of Addictions and Psychopharmacology affiliated with St. Petersburg State Pavlov Medical University and the Leningrad Regional Center of Addictions, Novo-Deviatkino 19/1, Leningrad Region 188661, Russia. E-mail: [email protected]. 88 The Heffter Review of Psychedelic Research, Volume 2, 2001 Experimental Design and Methods Information about the patients from the experimen- tal and control groups is in Table 1. There were 35 Design heroin addicts (27 male and 8 female) in the experi- Seventy detoxified heroin addicts were randomly mental group and 35 heroin addicts (28 male and 7 assigned to one of two groups. The patients of the ex- female) in the control group. There were no statisti- perimental group received psychotherapy in combi- cally significant differences between the experimental nation with a "psychedelic" dose of ketamine (2.0 mg/ and control groups with respect to age, duration of kg i.m.). The patients of the control group received heroin addiction, and duration of abstinence from the same psychotherapy combined with a very low, heroin. non-psychedelic (non-hallucinogenic), dose of Patients who participated in the study were mostly ketamine (0.20 mg/kg i.m.). This low dose induces young people (Table 1). In this respect it is important some pharmacological effects but without inducing a to note that heroin addiction has a higher prevalence peak psychedelic experience (see Results section be- among youth in Russia. The typical age of heroin ad- low). Both the psychotherapist and patient were blind dicts in Russia is between 17 and 26. The typical dura- to the dose of ketamine. All patients were treated alike tion of addiction is about 3-4 years. Many heroin ad- and were given the same preparation. The KPT ses- dicts die because of overdosage or get imprisoned sions, regardless of dosage, were given under similar within the first several years of using heroin. circumstances. All patients' psychological and clinical evaluation Psychotherapist during the treatment and follow-up period were per- Psychotherapy was provided by a psychotherapist formed by a clinician evaluator other than the psycho- (psychiatrist) specially trained in KPT. Only one KPT therapist providing KPT. This rater was also blind to session was carried out for each patient. the dose of ketamine. Patient selection Patients The following exclusion and inclusion criteria were Seventy heroin addicts were screened, evaluated, employed: and randomized in the study. Patients were recruited Inclusion criteria: from the in-patient department of Leningrad Regional • ICD-10/DSM-IV criteria of current heroin de- Center of Addictions. This is a regional center for the pendence, present for at least one year treatment of alcoholism and drug dependence with a • Age between 18 and 30 300-bed hospital. After they completed acute detoxi- • At least high school education fication, informed consent was obtained from all pa- • Abstinence from heroin and other substances of tients prior to acceptance into the study. All patients abuse for at least two weeks were accepted into the study as in-patients and dis- • Not currently on psychotropic medication charged from the hospital after they completed this • At least one relative willing to assist in follow- treatment. up and provide outcome data TableTabl 1.e 1Information. Informati abouton abo groupsut groups of patients. of pati Dataents .expr Daessedta exp asress MEANed as(SEM) MEAN (SEM) Information about patients Ketamine Dose Duration of heroin Duration of abstinence Age addiction (months) before KPT (days) High 23.03 (0.75) 31.66 (4.08) 25.29 (2.51) Low 21.63 (0.51) 37.37 (3.88) 24.54 (1.7) 89 Krupitsky, Ketamine-Assisted Psychotherapy • Stable address within St. Petersburg or nearest Psychiatric symptoms and psychopathology were district of Leningrad Region assessed with: • Home telephone number at which the patient • ICD-10 Structured clinical interview for psy- could be reached chiatric disorders (PSCI). • Not currently on probation • Zung self-rating depression scale (ZDS) (Zung, • Competency to give informed consent and oth- 1965) - to assess depression. erwise participate • Spielberger self-rating state-trait anxiety scale (SAS) (Spielberger et al., 1976) - to assess state Exclusion criteria: and trait anxiety. • ICD-10/DSM-IV criteria of organic mental dis- • Visual analog scale of craving (VASC) - 100 order, schizophrenic disorder, paranoid disor- mm line marked by subjects relative to the in- der, major affective disorder, and seizure dis- tensity of craving experienced while complet- order ing the scale. • ICD-10/DSM-IV criteria for alcoholism or • Scale of Anhedonia syndrome (SA) (Krupitsky polydrug dependency et al., 1998)--this scale was developed to as- • Advanced neurological, cardiovascular, renal, sess the severity of the syndrome of anhedonia. or hepatic diseases Many detoxified heroin addicts report that the • Pregnancy termination of withdrawal leads to a syndrome • Family history of psychiatric disorders listed of anhedonia which includes affective symp- above toms (mostly depression), anxiety, tension, ir- • Clinically significant cognitive impairment ritation, feeling like life is dull and empty, pas- • Active tuberculosis or current febrile illness sivity, sleep disturbance, and craving for heroin. • AIDS-defining illness SA has affective, cognitive, and behavioral • Significant laboratory abnormality such as se- subscales. vere anemia, unstable diabetes, or liver func- • Hallucinogenic Rating Scale (HRS) (Strassman tion tests >3X above normal et al., 1994)-to assess acute subjective response • Pending legal charges with potential impending to a psychoactive drug challenge. incarceration • Concurrent participation in another treatment Psychological assessments: study • Minnesota Multiphasic Personality Inventory • Concurrent treatment in another substance abuse (MMPI) (Dahlstrom et al., 1972)--to assess per- program sonality characteristics. Screening evaluation included: • Locus of Control Scale (LCS) developed by • Formal psychiatric examination Rotter (Phares, 1976) and adapted in Russia by • Standard medical examination, including blood Bazhin et al. (1993) - to assess the ability of the chemistry panel (including hepatic functions), patients to control and manage different situa- urine analysis, HIV-test, pregnancy test and tions in their lives. EKG • Color Test of Attitudes (CTA) (Etkind, 1980) - • Review of previous medical and psychiatric to assess nonverbal unconscious emotional at- records titudes. The methodology of CTA had been de- scribed in detail previously (Krupitsky and Assessment Instruments Grinenko, 1997). In choosing the battery of assessment