Ketamine Therapy for Methamphetamine Addiction

(KARE Trial)

Recruiting at 1 trial location

Overseen By SFDPH Center for Substance Use and Health

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Nicky Mehtani, MD, MPH

Must not be taking: Antipsychotics

Disqualifiers: Cognitive impairment, Psychosis, Hypertension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 13

Duration: 5 weeks

12 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to learn whether it is possible to use intramuscular (IM) ketamine in combination with psychotherapy to treat moderate-to-severe methamphetamine use disorder (MeUD) in publicly insured patients with or at-risk for HIV disease. The main questions it aims to answer are: * Do publicly insured patients find ketamine-assisted psychotherapy feasible and acceptable as a potential treatment for MeUD? * Is IM ketamine safe and tolerable among patients with MeUD? Participants will: * Receive 3 monitored doses of IM ketamine * Have 3 preparation and 4 integration psychotherapy visits * Report their daily amounts of methamphetamine used prior to, during, and up to 3 months following the intervention

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify that you need to stop taking your current medications. In fact, it mentions that you should continue your usual regimen of prescribed opioid-based medications and any routine mental health treatments outside of the trial.

What evidence supports the effectiveness of ketamine as a drug for methamphetamine addiction?

Research shows that ketamine has been effective in treating other addictions, like cocaine and alcohol, and has shown promise in psychiatric conditions such as depression. This suggests it might also help with methamphetamine addiction. ^{1 2 3 4 5}

Is ketamine generally safe for human use?

Ketamine has been used for many years and is known for its rapid effects, but it can have side effects like confusion and bladder issues. In studies for depression, it showed temporary side effects but was generally well-tolerated. ^{6 7 8 9 10}

How does ketamine therapy differ from other treatments for methamphetamine addiction?

Ketamine therapy is unique because it uses subanesthetic doses to induce psychedelic experiences, which may help in treating addiction by altering brain pathways related to dependence. Unlike traditional treatments, ketamine has shown promise in maintaining abstinence in other addictions, such as alcohol, and is being explored for its potential in methamphetamine addiction. ^{3 4 11 12 13}

Research Team

Nicky Mehtani, MD MPH

Principal Investigator

University of California, San Francisco

Eligibility Criteria

This trial is for individuals with moderate-to-severe methamphetamine addiction who are publicly insured and either have HIV or are at risk for it. Participants will receive ketamine injections and undergo psychotherapy sessions to see if this combination helps reduce their meth use.

Inclusion Criteria

Moderate or severe methamphetamine use disorder

I have HIV, have taken PrEP recently, or engaged in risky behavior.

Able and willing to provide informed consent and adhere to visit schedule

Exclusion Criteria

I have a tumor in my brain.

Engaged in a contingency management program during study

Active suicidal ideation with intent

Timeline

Screening

Participants are screened for eligibility to participate in the trial

Up to 4 weeks

1 visit (in-person)

Treatment

Participants receive 3 doses of intramuscular ketamine and 7 psychotherapy sessions over a 5-week period

5 weeks

10 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment with follow-up assessments at 4 and 12 weeks post-intervention

12 weeks

2 visits (in-person)

Treatment Details

Interventions

• Ketamine

Trial Overview The study tests the feasibility, acceptability, safety, and tolerability of intramuscular ketamine combined with psychotherapy as a treatment for methamphetamine use disorder in patients concerned with or at risk of HIV.

Participant Groups

Group I: Ketamine-Assisted Psychotherapy Experimental Treatment 2 Interventions

Participants will receive 3 administrations of intramuscular (IM) ketamine, dosed approximately once weekly, in combination with 7 psychotherapy visits over a 5-week treatment period. All ketamine dosing and psychotherapy visits will be conducted in-person in a designated therapy room.

Ketamine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Ketalar for:

• Anesthesia
• Treatment-resistant depression

Approved in European Union as Ketalar for:

• Anesthesia
• Treatment-resistant depression

Approved in United States as Spravato for:

• Treatment-resistant depression

Approved in European Union as Spravato for:

• Treatment-resistant depression

Approved in Canada as Spravato for:

• Treatment-resistant depression

Who Is Running the Clinical Trial?

Nicky Mehtani, MD, MPH

Lead Sponsor

Trials

1

Recruited

10+

San Francisco Department of Public Health

Collaborator

Trials

38

Recruited

36,000+

National Center for Advancing Translational Sciences (NCATS)

Collaborator

Trials

394

Recruited

404,000+

California HIV/AIDS Research Program

Collaborator

Trials

21

Recruited

2,800+

Findings from Research

In a study of 55 cocaine-dependent adults, a single infusion of ketamine significantly improved treatment outcomes, with 48.2% of participants maintaining abstinence compared to only 10.7% in the control group receiving midazolam.

Participants who received ketamine were 53% less likely to relapse and reported 58.1% lower craving scores throughout the trial, indicating that ketamine may effectively support behavioral modification efforts in treating cocaine dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Single Ketamine Infusion Combined With Mindfulness-Based Behavioral Modification to Treat Cocaine Dependence: A Randomized Clinical Trial. Dakwar, E., Nunes, EV., Hart, CL., et al.[2020]

In a European clinical trial, a 55-year-old male with treatment-resistant depression and substance use disorder showed significant improvement in depression symptoms after a single intravenous infusion of ketamine, with reductions in Hamilton Depression Rating Scale (HDRS) scores from 36 to 16 and Beck Depression Inventory (BDI) scores from 26 to 9.

The antidepressant effects of ketamine were rapid, with the patient reporting improvements just 25 minutes into the infusion, and these effects lasted for at least 7 days, demonstrating ketamine's potential as a fast-acting treatment for depression even in patients with co-occurring substance use disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous ketamine therapy in a patient with a treatment-resistant major depression. Liebrenz, M., Borgeat, A., Leisinger, R., et al.[2022]

Ketamine has shown potential benefits in treating psychiatric conditions like major depression and in supporting abstinence from alcohol and opiates, based on a literature review of studies from 2003 to 2013.

Despite its promising therapeutic effects, ketamine poses a risk of abuse and dependence, leading to various somatic, psychiatric, and cognitive complications, highlighting the need for careful consideration in its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Ketamine: psychiatric indications and misuses]. Delimbeuf, N., Petit, A., Karila, L., et al.[2015]

Ketamine, originally developed as an anesthetic, has gained popularity for recreational use due to its dissociative effects, leading to hallucinations and a feeling of detachment from reality.

Long-term use of ketamine can result in tolerance, dependence, and withdrawal symptoms, highlighting the risks associated with its recreational use despite its controlled status in medical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Ketamine--dreams and realities]. Arditti, J., Spadari, M., de Haro, L., et al.[2016]

In a study of 24 patients with major depressive disorder, activity in the pregenual anterior cingulate cortex (pgACC) was found to predict how well patients would respond to ketamine treatment, suggesting its importance in personalizing depression therapy.

The study also revealed that increased pgACC activity was linked to higher levels of glutamate 24 hours after ketamine infusion, which correlated with better clinical outcomes, indicating a potential biomarker for early treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predicting Antidepressant Effects of Ketamine: the Role of the Pregenual Anterior Cingulate Cortex as a Multimodal Neuroimaging Biomarker. Weigand, A., Gärtner, M., Scheidegger, M., et al.[2023]

Ketamine (KET) has been used recreationally since 1962 due to its rapid onset and unique dissociative effects, but its abuse can lead to serious physical and psychological side effects, particularly urological toxicity.

Methoxetamine (MXE), a newer derivative of KET, offers similar dissociative effects but may have even worse side effects, including mood disturbances and acute cerebellar toxicity, indicating it is not a safer alternative to KET.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

From "Special K" to "Special M": the evolution of the recreational use of ketamine and methoxetamine. Corazza, O., Assi, S., Schifano, F.[2022]

Ketamine and esketamine demonstrate rapid antidepressant effects, with improvements in clinical response observed within 40 minutes to 1 week for ketamine and 2 hours to 4 weeks for esketamine, along with reductions in depression scores and suicidality.

Despite their effectiveness, the long-term safety and efficacy of ketamine and esketamine remain uncertain, and the overall quality of the studies reviewed was critically low, highlighting the need for more rigorous research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of ketamine and esketamine for depression: an overview of systematic reviews with meta-analyses. Lima, TM., Visacri, MB., Aguiar, PM.[2022]

Subcutaneous (SC) administration of racemic ketamine and esketamine has shown rapid and robust antidepressant effects in both unipolar and bipolar patients, with response and remission rates ranging from 50% to 100% after single or multiple doses.

The studies indicated that SC ketamine is generally well-tolerated, with only transitory side effects, making it a promising and cost-effective treatment option for depression, especially in developing countries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous Ketamine in Depression: A Systematic Review. Cavenaghi, VB., da Costa, LP., Lacerda, ALT., et al.[2021]

Methoxetamine, a designer drug similar to ketamine, primarily affects the glutamatergic and serotonin receptors, leading to dissociative effects and potential renal and bladder toxicity, similar to those seen with ketamine.

Acute toxicity from methoxetamine can result in symptoms like dissociation, delirium, and cerebellar issues, and management requires supportive care, as it is not detectable in standard urine drug tests.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The ketamine analog methoxetamine: a new designer drug to threaten military readiness. Craig, CL., Loeffler, GH.[2019]

Ketamine hydrochloride has shown rapid and significant antidepressant effects in patients with treatment-resistant mood and anxiety disorders, although the studies supporting this have small sample sizes and limited long-term data.

While ketamine may offer benefits for some patients, there are important safety concerns and limitations in the existing research that must be considered when using it as an off-label treatment for psychiatric disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders. Sanacora, G., Frye, MA., McDonald, W., et al.[2022]

In a clinical trial, ketamine-assisted psychotherapy (KPT) significantly improved treatment outcomes for alcoholism, with 65.8% of patients achieving total abstinence for over a year, compared to only 24% in the conventional treatment group.

KPT appears to induce beneficial psychological changes, such as improved self-concept and life values, while also affecting neurotransmitter systems related to alcohol dependence, suggesting a multifaceted mechanism of action for its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine psychedelic therapy (KPT): a review of the results of ten years of research. Krupitsky, EM., Grinenko, AY.[2022]

The RTT-KaT program, which combines ketamine-assisted therapy with group psychotherapy, was well tolerated by all 128 participants, with no dropouts reported during the 12-week program.

While 49.16% of sessions noted elevated blood pressure post-treatment, most adverse effects were mild and transient, including nausea (12.05%), vomiting (2.52%), headaches (3.35%), and dizziness, indicating a good safety profile for ketamine use in this community setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of intramuscular and sublingual ketamine for psychiatric treatment in the Roots To Thrive ketamine-assisted therapy program: a retrospective chart review. Tsang, VWL., Tao, B., Dames, S., et al.[2023]

Ketamine, originally developed as an anesthetic, has gained popularity for recreational use due to its dissociative and hallucinogenic effects, leading to risks of acute intoxication and long-term issues like tolerance and dependence.

In France, ketamine is strictly regulated under narcotics legislation, and any theft of medical supplies must be reported to authorities, highlighting the need for control over its use and distribution.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine - reves et realites. Arditti, J., Spadari, M., de Haro, L., et al.[2016]

References

1. United States pubmed.ncbi.nlm.nih.gov

A Single Ketamine Infusion Combined With Mindfulness-Based Behavioral Modification to Treat Cocaine Dependence: A Randomized Clinical Trial. [2020]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Intravenous ketamine therapy in a patient with a treatment-resistant major depression. [2022]

3. Belgium pubmed.ncbi.nlm.nih.gov

[Ketamine: psychiatric indications and misuses]. [2015]

4. England pubmed.ncbi.nlm.nih.gov

[Ketamine--dreams and realities]. [2016]

5. England pubmed.ncbi.nlm.nih.gov

Predicting Antidepressant Effects of Ketamine: the Role of the Pregenual Anterior Cingulate Cortex as a Multimodal Neuroimaging Biomarker. [2023]

6. England pubmed.ncbi.nlm.nih.gov

From "Special K" to "Special M": the evolution of the recreational use of ketamine and methoxetamine. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Use of ketamine and esketamine for depression: an overview of systematic reviews with meta-analyses. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Subcutaneous Ketamine in Depression: A Systematic Review. [2021]

9. England pubmed.ncbi.nlm.nih.gov

The ketamine analog methoxetamine: a new designer drug to threaten military readiness. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Ketamine psychedelic therapy (KPT): a review of the results of ten years of research. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Safety and tolerability of intramuscular and sublingual ketamine for psychiatric treatment in the Roots To Thrive ketamine-assisted therapy program: a retrospective chart review. [2023]

13. England pubmed.ncbi.nlm.nih.gov

Ketamine - reves et realites. [2016]