Objective: To test the efficacy and safety of a single intravenous subanesthetic dose of ketamine for the treatment of PTSD and associated depressive symptoms in patients with chronic PTSD.

Results: Ketamine infusion was associated with significant and rapid reduction in PTSD symptom severity, compared with midazolam, when assessed 24 hours after infusion (mean difference in Impact of Event Scale–Revised score, 12.7 [95% CI, 2.5-22.8]; P = .02). Greater reduction of PTSD symptoms following treatment with ketamine was evident in both crossover and first-period analyses, and remained significant after adjusting for baseline and 24-hour depressive symptom severity. Ketamine was also associated with reduction in comorbid depressive symptoms and with improvement in overall clinical presentation. Ketamine was generally well tolerated without clinically significant persistent dissociative symptoms.

Conclusions and Relevance: This study provides the first evidence for rapid reduction in symptom severity following ketamine infusion in patients with chronic PTSD. If replicated, these findings may lead to novel approaches to the pharmacologic treatment of patients with this disabling condition.

Read full article here: https://jamanetwork.com/journals/jamapsychiatry/article-abstract/1860851

Abstract: Ketamine can be used in the treatment of opioid withdrawal symptoms. Here are two case discussions of treatment of withdrawal symptoms in opioid dependent patients undergoing detoxification. Our case reports endorse the hypothesis that N-methyl D-aspartate (NMDA) antagonists may selectively inhibit the expression of opiate withdrawal. The use of intravenous ketamine can be considered as a bridge to successful initiation of buprenorphine to wean the patient off from high opioid doses while providing adequate analgesia during the transition period. Read full article here. https://benthamopen.com/contents/pdf/TOPAINJ/TOPAINJ-4-1.pdf

Abstract: Ketamine is a prescription drug used for general anesthesia. In subanesthetic doses, it induces profound psychedelic experiences and hallucinations. The subanesthetic effect of ketamine was the hypothesized therapeutic mechanism in the authors' use of ketamine-assisted psychotherapy for alcoholism. The results of a controlled clinical trial demonstrated a considerable increase in efficacy of the authors' standard alcoholism treatment when supplemented by ketamine psychedelic therapy (KPT). Total abstinence for more than one year was observed in 73 out of Ill (65.8%) alcoholic patients in the KPT group, compared to 24% (24 out of 100 patients) of the conventional treatment control group (p<0.01). The authors' studies of the underlying psychological mechanisms of KPT have indicated that ketamine-assisted psychedelic therapy of alcoholic patients induces a harmonization of the Minnesota Multiphasic Personality Inventory (MMPI) personality profile, positive transformation of nonverbalized (mostly unconscious) self-concept and emotional attitudes to various aspects of self and other people, positive changes in life values and purposes. important insights into the meaning of life and anincrease in the level of spiritual development. Most importantly, these psychological changes were shown to favor a sober lifestyle. The data from biochemical investigations showed that the phannacological action of KPT affects both monoaminergic and opioidergic neurotransmitter metabolism, i.e., those neurochemical systems which are involved in the pathogenesis of alcohol dependence. The data from EEG computer-assisted analysis demonstrated that ketamine increases theta activity in cerebrocortical regions of alcoholic patients. This is evidence of the reinforcement of limbic cortex interaction during the KPT session. Read full article here. https://www.tandfonline.com/doi/abs/10.1080/02791072.1997.10400185

Abstract: Current research suggests that ketamine-assisted psychotherapy has benefit for the treatment of mental disorders. We report on the results of ketamine-assisted intensive outpatient psychotherapeutic treatment of a client with treatment-resistant, posttraumatic stress disorder (PTSD) as a result of experiences of racism and childhood sexual abuse. The client’s presenting symptoms included hypervigilance, social avoidance, feelings of hopelessness, and intense recollections. These symptoms impacted all areas of daily functioning. Psychoeducation was provided on how untreated intergenerational trauma, compounded by additional traumatic experiences, potentiated the client’s experience of PTSD and subsequent maladaptive coping mechanisms. Ketamine was administered four times over a 13-day span as an off-label, adjunct to psychotherapy. Therapeutic interventions and orientations utilized were mindfulness-based cognitive therapy (MBCT) and functional analytic psychotherapy (FAP). New skills were obtained in helping the client respond effectively to negative self-talk, catastrophic thinking, and feelings of helplessness. Treatment led to a significant reduction in symptoms after completion of the program, with gains maintained 4 months post-treatment. This case study demonstrates the effective use of ketamine as an adjunct to psychotherapy in treatment-resistant PTSD. Read full article here. https://journals.sagepub.com/doi/full/10.1177/1534650121990894

Conclusion: The results of this double-blind randomized clinical trial of KPT for heroin addiction showed that highdose (2.0 mg/kg) ketamine psychedelic psychotherapy (KPT) elicits a profound, full psychedelic experience in heroin addicts. On the other hand, low-dose KPT (0.20 mg/kg) elicits "sub-psychedelic" experiences that are very similar to ketamine-facilitated guided imagery. Highdose KPT produced a significantly greater rate of abstinence in heroin addicts within the first six months of follow-up than did low-dose KPT. High-dose KPT brought about a greater and longer-lasting reduction in craving for heroin, as well as greater positive change in nonverbal unconscious emotional attitudes.

Thus, it is possible that the higher rate of abstinence in the high-dose group was to some extent due to positive effects of ketamine on craving (which has been reported with other NMDA receptor ligands). It also may be due to the positive transformation of nonverbal unconscious emotional attitudes. Read full article here. https://www.researchgate.net/profile/Evgeny-Krupitsky/publication/266249375_Ketamine-Assisted_Psychotherapy_KPT_of_Heroin_Addiction_Immediate_Effects_and_Six_Months_Follow-Up/links/57cf7a8608ae057987ac0e23/Ketamine-Assisted-Psychotherapy-KPT-of-Heroin-Addiction-Immediate-Effects-and-Six-Months-Follow-Up.pdf

Results and conclusion: Seven completed studies were identified. Two studies focused on alcohol use disorder, two focused on cocaine use disorder, and three focused on opioid use disorder. Both cocaine studies found improvements in craving, motivation, and decreased cocaine use rates, although studies were limited by small sample sizes, a homogeneous population and short follow-up. Studies of alcohol and opioid use disorders found improvement in abstinence rates in the ketamine group, with significant between-group effects noted for up to two years following a single infusion, although these were not placebo-controlled trials. These results suggest that ketamine may facilitate abstinence across multiple substances of abuse and warrants broader investigation in addiction treatment. We conclude with an overview of the six ongoing studies of ketamine in the treatment of alcohol, cocaine, cannabis, and opioid use disorders and discuss future directions in this emerging area of research. Read full article here. https://www.frontiersin.org/articles/10.3389/fpsyt.2018.00277/full

Abstract: Ketamine is a dissociative anaesthetic drug which acts on the central nervous system chiefly through antagonism of the n-methyl-d-aspartate (NMDA) receptor. Recently, ketamine has attracted attention as a rapid-acting anti-depressant but other studies have also reported its efficacy in reducing problematic alcohol and drug use. This review explores the preclinical and clinical research into ketamine's ability to treat addiction. Despite methodological limitations and the relative infancy of the field, results thus far are promising. Ketamine has been shown to effectively prolong abstinence from alcohol and heroin in detoxified alcoholics and heroin dependent individuals, respectively. Moreover, ketamine reduced craving for and self-administration of cocaine in non-treatment seeking cocaine users. However, further randomised controlled trials are urgently needed to confirm ketamine's efficacy. Possible mechanisms by which ketamine may work within addiction include: enhancement of neuroplasticity and neurogenesis, disruption of relevant functional neural networks, treating depressive symptoms, blocking reconsolidation of drug-related memories, provoking mystical experiences and enhancing psychological therapy efficacy. Identifying the mechanisms by which ketamine exerts its therapeutic effects in addiction, from the many possible candidates, is crucial for advancing this treatment and may have broader implications understanding other psychedelic therapies. In conclusion, ketamine shows great promise as a treatment for various addictions, but well-controlled research is urgently needed. Read full article here. https://www.sciencedirect.com/science/article/abs/pii/S0028390818300170

Abstract: The N-methyl-D-aspartate receptor antagonist ketamine has rapid onset activity in treatment-resistant depression, post-traumatic stress disorder and obsessive compulsive disorder. Due to similarities in brain network activity in depression and anxiety disorders, we hypothesized that ketamine might also be active in other refractory anxiety disorders. We evaluated the efficacy and safety of ketamine in 12 patients with refractory generalized anxiety disorder and/or social anxiety disorder who were not currently depressed, using an ascending single dose study design (0.25, 0.5, 1 mg/kg administered subcutaneously) at weekly intervals. Within 1 h of dosing, patients reported reduced anxiety, which persisted for up to seven days. A dose-response profile was noted for anxiolytic effects, dissociative side effects, and changes in blood pressure and heart rate, with minor changes at 0.25 mg/kg, and progressively greater and more durable changes at the higher doses. Ten of 12 patients were treatment responders at 0.5–1 mg/kg. Ketamine was safe and well tolerated in this population. Ketamine may be a potential therapeutic alternative for patients with refractory generalized anxiety disorder/social anxiety disorder. Along with its demonstrated effectiveness in patients with treatment-resistant depression, obsessive compulsive disorder and post-traumatic stress disorder, these data raise the intriguing possibility that ketamine may have broad efficacy in disorders characterized by negative emotional states, and that these disorders may share a common precipitating neurobiology. Read full article here. https://journals.sagepub.com/doi/abs/10.1177/0269881117705089

Abstract

In summary, the dual action of Ketamine leads to a unique constellation of dopamine driven positive reinforcement, but low addiction liability.