The Effects of Minocycline in Opioid-maintained Patients

Sixty completers will be recruited through the VA methadone clinic, as well as through the
APT Foundation Methadone Maintenance Program. After the initial phone screening, potential
subjects will undergo a comprehensive evaluation which will include medical, psychiatric, and
drug use histories as well as physical, psychiatric, and laboratory examinations. Laboratory
examination will include CBC, liver and thyroid function tests, serum electrolytes, BUN,
creatinine, PT, PTT, urine analysis (including urine pregnancy for women) and urine
toxicology screening.

Participants will be terminated from the study following opioid relapse, or use of any other
psychotropic medications. If participants are noncompliant (no-show, positive urine
screening, noncompliance with medication protocol/missing more than one dose of
minocycline/placebo), participation will be terminated.

This double-blind, randomized clinical trial will randomize male and female veterans and
non-veterans currently undergoing methadone maintenance treatment for opioid dependence to
either minocycline (200mg/day) or placebo for 15 days. Upon inclusion, participants will be
subjected to a pain assessment to evaluate baseline pain thresholds and tolerance: the Cold
Pressor Test. An experimental treatment of either minocycline or placebo will then be
initiated and maintained for 15 days. Additionally, at the beginning of Week 2 of treatment,
participants will be given a Personal Digital Assistant (PDA) an HP iPAQ Pocket PC 2003 Pro
that will administer Ecological Momentary Assessments (EMA). Using EMA, we can assess change
in pain sensitivity, withdrawal symptoms and cognitive performance in the participants'
natural environment, which increases the ecological validity of the study. Participants will
be asked to return to the laboratory several times a week for the 15 consecutive days that
they are taking minocycline in order to receive the study medication and to assess changes in
pain thresholds and tolerance (i.e. to assess the presence, or lack thereof of hyperalgesia).
Upon completion of experimental treatment, participants will be asked to return a final time
to undergo pain measurement once more, to assess any changes in pain sensitivity after
completion of minocycline.

Inclusion Criteria:

- Males and females, between the ages of 18 and 55

- Diagnosed with opioid dependence and currently enrolled in methadone maintenance
treatment

- Compliant in methadone maintenance treatment and on a stable dose for two weeks or
greater

- No current dependence or abuse of any other drugs (other than tobacco or marijuana)

- No current medical problems

- For women:

- not pregnant as determined by pregnancy screening;

- not breast feeding; u

- using acceptable birth control methods;

- not experiencing moderate to severe premenstrual symptoms (may interfere with
pain assessment);

- regular menstrual cycles

Exclusion Criteria:

- Current major psychiatric illnesses including mood, psychotic, or anxiety disorders

- History of major medical illnesses, including liver diseases, heart disease, or other
medical conditions that the physician investigator deems contraindicated for inclusion
in the study

- Current use of over-the-counter or prescription psychoactive drugs (including regular
use of NSAIDS, antidepressant, anxiolytics, antipsychotics, mood stabilizers,
psychostimulants) or drugs that would be expected to have major interactions with
drugs to be tested, e.g., benzodiazepines, codeine, Percocet, and other opiate drugs

- Liver function tests (ALT or AST) greater than 3x normal

- Allergy to minocycline or other tetracyclines