Results have been published from a first-of-its-kind clinical trial testing the effectiveness of ketamine infusions, combined with psychotherapy, in reducing the rate of relapse in people with severe alcoholism who have recently been detoxified. The landmark trial found ketamine-assisted psychotherapy was more effective at maintaining long-term alcohol abstinence than any other current treatment.
The new study, published in the Journal of American Psychiatry, reports on a Phase 2 randomized controlled trial, dubbed KARE (Ketamine for the Reduction of Alcoholic Relapse). The trial recruited 96 adults with severe alcohol use disorder who were currently abstinent after participating in a detox program.
The cohort was randomly split into four groups: ketamine and psychotherapy, ketamine and alcohol education, placebo and psychotherapy, or placebo and alcohol education. Each subject received three weekly infusions of either placebo or ketamine, accompanied by seven one-hour sessions of either psychotherapy or education about the risks of alcohol use. The primary outcome measures were tracking overall relapse rates and total days abstinent six months after the treatment.
The results show the ketamine plus psychotherapy group displayed the highest abstinence rates out of the four groups after six months. Compared to the placebo with alcohol education group, ketamine-assisted psychotherapy was 2.5 times more likely lead to abstinence at the six month follow-up.
“Alcoholism can destroy lives, and we urgently need new ways to help people cut down,” explains Celia Morgan, lead author on the new study. “We found that controlled, low doses of ketamine combined with psychological therapy can help people stay off alcohol for longer than placebo. This is extremely encouraging, as we normally see three out of every four people returning to heavy drinking within six months of quitting alcohol, so this result represents a great improvement.”
Interestingly, ketamine plus alcohol education led to slightly better results looking at overall days abstinent compared to the placebo plus psychotherapy group. Morgan is, however, clear to note this does not suggest ketamine can be safely or effectively self-administered outside of clinical contexts.
“We’re certainly not advocating taking ketamine outside of a clinical context,” says Morgan. “Street drugs come with obvious risks, and it’s the combination of a low dose of ketamine and the right psychological therapy that is key, as is the expertise and support of clinical staff. This combination showed benefits still seen six months later, in a group of people for whom many existing treatments just don’t work.”
Morgan is also cautious to not overstate her team’s findings. Given was still a relatively small Phase 2 trial, she says more work is needed to confirm these results in bigger cohorts.
How does it work?
It is still unclear exactly how ketamine could be exerting its beneficial effects in the context of addiction therapy. Research into the rapid anti-depressant qualities of ketamine has discovered the drug generates unique effects on the brain. One incredible study from 2019 even suggested ketamine could be used to “edit addiction memories” in the brain.
The researchers behind this new study indicate there seems to be a synergistic effect to the combination of ketamine and psychotherapy, leading to beneficial therapeutic outcomes exceeding anything seen with each element alone. This suggests the efficacy of ketamine in this context sits much more in a traditional frame of psychedelic-assisted psychotherapy, where the strength of a transformative "mystical" experience is what powers the therapeutic outcomes.
Not only did I get a life changing and mind-altering experience, but then the therapist did plug some new thoughts to me that made me think differently
Merve Mollaahmetoglu, a University of Exeter researcher working on the study, says the subjective responses from participants in the trial indicate the “mystical experience” of a ketamine session tends to amplify beneficial insights into addictive behaviors.
“The experiences people describe after taking ketamine infusions suggest the drug gives a new perspective that may be helpful in psychological therapy,” says Mollaahmetoglu. “Ketamine induces a sense of being outside of your body that some say can stimulate an ‘observer state’ similar to that described in mindfulness, which may help patients take a step back, and consider thoughts and emotions. Participants told us this experience helped change their relationship with alcohol.”
A study published last year in the journal frontiers in Psychiatry offered a qualitative exploration of subjective ketamine experiences from 12 participants in the KARE trial. That study hypothesized a ketamine-induced sense of awe and connectedness could play a role in helping break the compulsive thought patterns commonly seen in alcohol use disorder.
“Acute ketamine experiences reported by patients—feelings of connectedness, altered time perception, self-diminishment, perceived vastness, and physical sensations—all map on to the experience of “awe” which is an increasingly researched psychological construct,” the researchers wrote in last year’s study. “Awe has been proposed as a potential mechanism of action underlying the effects of classic psychedelic-assisted psychotherapy and theoretically overlaps with mystical experiences, the small self and ego dissolution and challenging experiences under psychedelics.”
Affirming the importance of combining ketamine with psychotherapy, several trial participants anecdotally noted the value of therapy following their active drug sessions. This balancing of a mystical experience with integrative therapy sessions has been previously cited as crucial for other psychedelic medicines such as MDMA for PTSD or psilocybin for depression.
“Not only did I get a life changing and mind-altering experience, but then the therapist did plug some new thoughts to me that made me think differently,” said one of the ketamine trial participants. “I feel that it is really important that when you are split open, you know, in such an intense and life changing way that you are given new thoughts and you know that someone gives you something to refill that, so you do change stuff.”
Biotechnology company AWAKN has partially funded these explorations into the efficacy of ketamine for alcohol addiction. Because ketamine is already an approved drug this therapy can technically be rolled out in public clinics immediately. AWAKN is working with Morgan and other researchers to utilize the KARE trial data and deliver ketamine-assisted therapy in clinics across the UK and Europe.
The new study was published in the Journal of American Psychiatry.
Source: University of Exeter
