Ketamine-Assisted Recovery for Methamphetamine Use Disorder & HIV

Inclusion Criteria:

• Age 18-69

• Moderate or severe methamphetamine use disorder

• Interest in reducing or stopping methamphetamine use

• Insured by MediCal, MediCare, or Healthy San Francisco

• Used methamphetamine ≥7 out of the 30 days prior to screening OR enrolled in aresidential drug treatment program

• Have a diagnosis of HIV OR taken PrEP over the last 90 days OR engaged in ≥1 riskbehavior for HIV acquisition/transmission over the last 90 days (i.e., anal sexunder the influence of methamphetamine, condomless sex with a partner ofserodiscordant or unknown HIV status, or any shared use of injection drug supplies)

• English speaking

• Permanently housed for ≥30 days OR enrolled in residential drug treatment for ≥5days

• Have a text-capable cell phone or access to email (if not enrolled in residentialtreatment)

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

• If necessary, willing to be contacted on a daily basis by one of the therapists for 7 days after each ketamine session

• Prior to scheduled ketamine sessions, agree: (a) abstain from using methamphetamineand cocaine for ≥48 hours, (b) abstain from using non-prescribed opioids, cannabisproducts, benzodiazepines, or alcohol for ≥24 hours, (c) consume no more than amodest quantity (e.g., 1 cup) of caffeine (e.g., coffee or tea) in the morning; (d)continue usual regimen of routinely prescribed opioid-based medications throughouttrial; and (e) continue any routine behavioral or pharmacologic mental healthinterventions as usual outside of the trial

• Female-born participants of child-bearing potential with male-born partners andmale-born participants with female-born partners of child-bearing potential mustagree to use highly effective contraception for at least 1 month prior to and 2months after ketamine administration

Exclusion Criteria:

• Significant prior use of ketamine for non-anesthetic purposes, as determined by theinvestigators

• Cognitive impairment sufficient to impede the ability to complete study tasks

• Lifetime history of intracranial hemorrhage

• Has an intracranial mass

• Had a stroke in the past 12 months

• Had a seizure in the past 6 months

• Has current psychosis or any lifetime history of schizophrenia or schizoaffectivedisorder

• Engaged in a contingency management program during study

• Taking any prohibited medications

• If receiving any medication that may cause blunting of responses or diminishedaffect, such as antipsychotics, exclusion will be as per the evaluation of the PIand study staff

• Active suicidal ideation with intent

• Baseline hypertension (≥150 SBP or ≥90 DBP) after repeated measurements

• History of aneurysmal vascular disease, dissection or arteriovenous malformation

• Had a cardiac arrest or myocardial infarction in the past 12 months

• QTc >450 msec on 12-lead EKG (Bazett's formula)

• Has a clinically significant arrhythmia

• Meets any of the following laboratory parameters: ALT ≥3x ULN, AST ≥3x ULN, totalbilirubin ≥1.5x ULN, eGFR <30mL/min by CKD-EPI or currently on dialysis

• Pregnant, breastfeeding, or unwilling to use birth control during the study

• Pending legal proceedings with a high risk for incarceration during the study

• Taken another investigational drug in the past 30 days

• Has any physical or mental health condition which, per the clinical judgment of theinvestigators, interferes with safe study participation or adherence to studyprocedures