Pharmacogenetics of Naltrexone for Stimulant Abuse
Condition: Substance Use Disorders; Methamphetamine Abuse
MeSH terms: Substance-Related Disorders
Intervention: Intranasal Methamphetamine
Intervention description: Intranasal Methamphetamine HCL administered at a dose of 30mg per 70 kg of the participants' body weight)
Intervention MeSH terms: Methamphetamine
Phase: Phase 2
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Participants will complete two testing sessions in which the effects of oral naltrexone (0 mg & 50 mg) will be tested in combination with intranasal methamphetamine. Participants will complete two testing sessions (naltrexone 0 mg + Methamphetamine & naltrexone 50 mg + methamphetamine), in randomized order.
Masking: Single (Participant)
Masking description: Participants and study staff conducting the lab sessions will be blinded to the treatment condition (i.e., naltrexone 0 mg or 50 mg)
Enrollment: 18.0
Sex: All
Minimum age: 21 Years
Maximum age: 50 Years
Healthy volunteers: No

Summary:

      This investigation will be the first study assessing genetic modulation of naltrexone's NTX
      effects upon the abuse liability of a stimulant drug (methamphetamine). The study team will
      assess the ability of oral NTX to block the reinforcing and positive subjective effects of
      intranasal (IN) methamphetamine (30mg/70kg). This investigation could identify an important
      Gene x Pharmacological interaction, contributing to the personalization of stimulant abuse
      pharmacotherapy.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female age 21 to 50 years

          2. DSM-5 criteria for mild-to-severe stimulant use disorder, along with intravenous,
             intranasal or smoked use of amphetamine-type stimulants in amounts equal to or greater
             than administered in the current study.

          3. Able to give written informed consent to participate.

          4. Females must be either post-menopausal, surgically sterilized, or using an acceptable
             method of contraception (double-barrier method like a condom with a spermicidal
             lubricant) to participate in this study.

          5. Racially Caucasian or of European descent.

        Exclusion Criteria:

          1. Currently seeking treatment for a substance use disorder.

          2. DSM-5 criteria for moderate-to-severe substance use disorders (except those involving
             cocaine, amphetamines and nicotine).

          3. Psychiatric condition that may affect the participants' ability to provide informed
             consent (e.g., psychotic disorder), or make participation hazardous for the
             participant or study staff (e.g., severe depression/suicidality, or risk of violence).

          4. Uncontrolled neurological, cardiovascular, and hepatic diseases, active tuberculosis,
             or any other disorder that might make administration of study medications hazardous.

          5. Gastrointestinal or renal disease that would significantly impair absorption,
             metabolism or excretion of study drug, or require medication or medical treatment.

          6. Current treatment with a psychotropic medication that in the physician's judgement
             would interfere with the study endpoints.

          7. History of allergy, adverse reaction, or sensitivity to amphetamines.

          8. Medical conditions that may make study participation hazardous:

               -  History of seizures or cardiac risk conditions (unstable angina, cardiac
                  arrhythmias, chest pain, strong palpitations (subjectively defined as the feeling
                  that the heart is beating too hard, too fast, skipping a beat, or fluttering).

               -  Elevated liver function tests (i.e., AST and ALT > 3 times the upper limit of
                  normal).

               -  Impaired renal function (creatinine > 1.2).

               -  Hypertension (>140/90).

               -  Asthmatic symptoms within the past 3 years.