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INNOSC Theranostics and
Pharmacological Sciences Ketamine for cocaine use disorder

individuals who reached the low-frequency level at EOT in increasing abstinence rates compared to a placebo.
had similar outcomes as those who reduced to abstinence However, it does not significantly affect the frequency or
and significantly better outcomes than those who remained amount of cocaine use compared to placebo, although it
at the high-frequency level. Specifically, at 12-month does reduce the frequency of cocaine use when compared
follow-up, participants with at least one level of reduction at to naltrexone. 23,120
EOT displayed fewer psychological problems, employment Ketamine, however, has several potential advantages
issues, and cocaine use days. This study demonstrates that for managing CUD. Like all other medications mentioned,
cocaine use reduction can improve overall well-being ketamine has been shown to reduce cocaine cravings and
in the long term. Considering these results, reduced use promote abstinence in multiple clinical trials. In the
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should become an acceptable treatment objective in CUD meantime, its rapid antidepressant effects may help
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interventions.
CUD patients cope with withdrawal-related depressive
Supporting this perspective, the Substance Abuse and symptoms, aiding in remission. In addition, ketamine
Mental Health Service administration released an advisory targets NMDARs to modulate the DAergic pathway,
in 2023 encouraging “low barrier care,” which emphasizes offering an alternative for individuals unresponsive to other
harm reduction by setting substance use reduction – not treatments. Therefore, compared to other treatments often
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abstinence – as a primary goal. This is supported by associated with barriers such as stigma, addiction risk, and
the U.S. FDA’s guidance stating that outcomes other than limited accessibility, ketamine’s unique properties and
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total abstinence are acceptable endpoints for cocaine rapid action make it a promising alternative for reducing
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addiction clinical trials. While abstinence remains the the harm associated with CUD.
ideal goal, participants with high use at baseline may deem
abstinence as unattainable. The introduction of reduced 9. Conclusion
use as a primary goal could motivate cocaine-dependent Subanesthetic ketamine shows promise as a
individuals to work gradually toward abstinence. Given its pharmacological intervention for CUD. Growing evidence
potential to reduce cocaine use and the clinical validity of highlights its ability to reduce cocaine consumption
reduction as an outcome, subanesthetic ketamine should be in dependent individuals. Pre-clinical research has
regarded as a promising pharmacological option for CUD. demonstrated that a single subanesthetic dose of ketamine
8. Ketamine versus other pharmacotherapy can reduce cue-induced craving, suppress drug-seeking
behaviors, and increase executive control over reward-
as CUD harm-reduction strategy based decision-making. 22,19 Furthermore, human subjects
At present, the standard treatment for CUD primarily exhibited decreased cocaine self-administration, craving,
involves psychosocial treatments, which include cognitive and enhanced motivation to quit cocaine after a single
behavioral therapy, motivational interviewing, and group ketamine infusion. 31,24
drug counseling. Although there are no current FDA- Although ketamine reduces cocaine misuse, there is
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approved therapeutical treatments for CUD, several mixed evidence that subanesthetic ketamine leads to long-
medications have been used for their off-label effects on term abstinence. However, recent findings suggest that a
patients who do not respond well to psychosocial therapies. reduction in cocaine consumption is as clinically significant
For instance, topiramate, an anti-seizure medication as achieving abstinence. 113,114 Thus, even if sobriety remains
that activates GABA and decreases dopamine release, is the ultimate objective, reduced cocaine use should be
sometimes used at low doses to augment CUD psychosocial considered a valuable measure of improvement in CUD
treatment. 117,118 Some studies find it more effective than a treatment.
placebo in reducing weekly cocaine use and suppressing Despite ketamine’s potential for abuse, its context-
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the reinforcing effects of cocaine. However, conflicting dependent nature allows for the safe administration of
clinical trial results indicate that further research is needed subanesthetic ketamine to individuals with CUD under
to confirm its effectiveness. Another option for patients the supervision of health-care professionals, similar to
unresponsive to topiramate is long-acting amphetamines. the use of Spravato as depression therapy. 19,26,122 Before
Although clinical trials did find them effective in reducing integrating subanesthetic ketamine as a harm-reduction
cocaine use, most trials reported poor retention rates. strategy for CUD into clinical practice, additional research
In addition, as a DAT inhibitor similar to cocaine, must delineate ketamine’s mechanism of action against
amphetamine’s risk of misuse cannot be overlooked. 117 cocaine. Current research suggests that ketamine may
Another medication, disulfiram, traditionally used alleviate CUD by modulating the dopaminergic system
to treat alcohol dependence, has shown some efficacy by altering dopamine levels directly, increasing BDNF

Volume 8 Issue 1 (2025) 39 doi: 10.36922/itps.4458