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Substance Use

for Health Care Providers

Substance Use

Note: Some medications mentioned in this chapter may not be available on the VHA National Formulary. Consult VA pharmacists for alternatives.

Key Points

  • Substance use disorders (SUDs) are common among people who are HIV infected: 40% of HIV-infected individuals in the United States are associated with injection drug use (IDU), either directly or by having an IDU sex partner.
  • Among injection drug users in the United States, 40-45% are HIV infected.
  • Substance use is a significant cause of morbidity and mortality in itself, and it is associated with HIV transmission and acquisition.
  • Ask all patients about any current or recent use of illicit drugs or alcohol, or misuse of prescription drugs. Ask specifically about injection drugs, opioids, methamphetamines, cocaine, and "club drugs."
  • At each visit, ask the patient directly about his or her substance use. Ask patients about their perceptions of IMPORTANCE of the issue and their CONFIDENCE in making any kind of change.
  • A comprehensive treatment program includes the care of medical providers, psychiatrists to assist with comorbid psychiatric conditions, social workers, housing counselors, case managers, and substance abuse counselors. Group therapy with peer support also may be important.
  • Treatment options exist along a continuum and include detoxification, treatment of comorbid conditions, maintenance of treatment, and prevention of relapse.


  • Substances frequently abused in the United States include alcohol, nicotine, cannabis, prescription medications (narcotics, sedatives, and many others), cocaine, heroin, methamphetamines, tranquilizers, hallucinogens, anabolic steroids, inhalants, and "club drugs."
  • Club drugs include methylenedioxymethamphetamine (MDMA, or ecstasy), flunitrazepam (Rohypnol), gamma-hydroxybutyrate (GHB), and ketamine.
  • The focus of this chapter is on recognition and management of abuse involving heroin, other opiates, and methamphetamine. Abuse of cocaine, cannabis, and club drugs will be addressed briefly.
  • Alcohol misuse and tobacco use are discussed in separate chapters (see Alcohol Misuse and Smoking Cessation.)

Veterans with HIV*

Alcohol use disorder: 33%

Illicit drug use: 30%

Other drug use: 22%

* Veterans in the VA HIV Clinical Case Registry in care in 2007 who had an ICD-9 code corresponding to these conditions


Addiction: a primary, chronic, neurobiologic disease, with genetic, psychosocial, and environmental factors influencing its development and manifestations. It is characterized by behaviors that include one or more of the following: impaired control over substance use, compulsive use, continued use despite harm, and craving.

Physical dependence: a state of adaptation that is manifested by a drug class-specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood level of the drug, or administration of an antagonist.

Tolerance: a state of adaptation in which exposure to a drug induces changes that result in a diminution of one or more of the drug's effects over time.

Substance dependence: a maladaptive pattern of substance use, leading to clinically significant impairment or distress, manifested as tolerance (need for increased amounts of the substance or decreased effect with the same amount) or withdrawal symptoms.

Substance abuse: a maladaptive pattern of substance use that has become socially, legally, or occupationally problematic for an individual.

SUD: a more general term comprising substance dependence or abuse.

IDU: includes IV drug use, IM drug use, and skin popping. IDU can involve opiates, methamphetamines, cocaine, sedatives/tranquilizers, or other drugs.


  • Drug abuse is closely associated with HIV infection in the United States: 40-45% of injection drug users are HIV infected, and 25-30% of noninjection drug abusers are HIV infected.
  • About 40% of people who are HIV infected are associated with IDU, either directly or by having an IDU sex partner.
  • In the United States, 60% of injection drug users are men, 45% are white, 43% have completed high school, and 53% are employed.
  • Comorbidities are common: 30% of injection drug users in the United States are PPD positive, 80-90% are infected with hepatitis C, 40% are infected with hepatitis B, and 60% use alcohol.
  • Drug abusers are at high risk of unsafe sex practices. For example, cocaine abusers are more likely to involve themselves in prostitution and unsafe sex in order to obtain money for drugs.
  • At least one third of drug abusers have an overt psychiatric comorbidity.

Substance Abuse, HIV Infection, and ART

  • Cocaine use decreases CD4 cell production by as much as 3- to 4-fold and increases the rate of HIV viral replication by up to 20-fold.
  • In a prospective cohort study, active drug use was strongly associated with underutilization of ART, nonadherence, and inferior virologic and immunologic responses to ART, compared with former drug use and nonuse of drugs.
  • Methamphetamine and cocaine binges are associated with interruptions in ART adherence.
  • A recent national survey showed that 23% of health providers for HIV-infected patients have a negative attitude toward treating HIV-infected IDU patients. These providers are less likely to prescribe ARVs to their IDU patients even when the patients meet criteria for starting ART.


There are many reasons to identify patients who abuse substances, and to try motivating them toward treatment. Unlike the strong evidence on effectiveness of brief interventions for alcohol misuse, there is little evidence from primary care settings that screening and brief interventions are effective for those with other drug-use disorders. Approaches that focus on the effects of substance abuse on the patient?s own health (eg, in terms of poor ART adherence, acquisition of infections) may be useful. See also Prevention for Positives.


At initial visit and at least annually thereafter: Ask all patients about any current or recent use of illicit drugs (in addition to alcohol and nicotine), including IDU, opioids, methamphetamines, cocaine, club drugs, illegally obtained prescription drugs, and legally obtained but misused prescription drugs. Check for comorbid psychiatric illnesses.


  • Goals for patients: Return to productive functioning.
  • Goals for providers: Reduce stigma and treatment bias.
  • Treatment includes helping the patient accept the role of having an illness, detoxification, treatment of comorbid conditions, maintenance of treatment, and relapse prevention.
  • Treatment ideally involves a comprehensive program of behavioral interventions, though many patients may not accept referral.
  • Comprehensive treatment may reduce drug abuse by 40-60%, reduce associated crime by 40-60%, and increase employment prospects by 40%.
  • A comprehensive treatment program incorporates the expertise of medical providers, psychiatrists to assist with comorbid psychiatric conditions, social workers, housing counselors, case managers, and substance abuse counselors. Group therapy with peer support can also be an important component of treatment.
  • For patients unwilling to undertake treatment, continue to address their substance use, focusing on reducing use or increasing readiness for drug cessation.

Brief Interventions for Patients Identified with SUD

At each visit, ask the patient directly about substance use. A useful technique for facilitating a patient-centered conversation about the readiness to change is to ask questions about the patient's perception of IMPORTANCE of the issue and his or her CONFIDENCE in making any kind of change.

Raise Importance

Ask: "On a scale of 1-10, how IMPORTANT is it for you to change your substance use?"

  • "Why did you give it (number) and not a (lower number)?"
  • "What would it take for you to give it a (higher number)?"

Raise Confidence

Ask: "On a scale of 1-10, how CONFIDENT are you that you can change successfully?"

  • "Why did you give it (number) and not a (lower number)?"
  • "What would it take for you to give it a (higher number)?"

Brief Interventions

Management of Specific Substance Use Disorders

(Print table)

Heroin and other opioids
Behavioral Interventions
  • In addition to brief primary care provider interventions suggested above, refer for specialty evaluation and treatment, or to substance abuse counselors in community-based organizations, rehabilitation facilities, and methadone maintenance sites.
  • Specific psychosocial interventions for opioid use have not demonstrated consistent efficacy.
  • If the patient is in withdrawal, or at high risk of withdrawal, refer for detoxification or to an emergency department. If unstable (medically or psychiatrically), refer to an emergency department.
  • For local (non-VA) substance abuse resources: 800-662-HELP.
  • Narcotics AnonymousLink will take you outside the VA website. VA is not responsible for the content of the linked site. provides group support.
  • Counsel on safe injection practices and needle exchange options, to reduce the risk of transmission of HIV and other bloodborne pathogens.
Pharmacologic Interventions
  • Treat comorbid psychiatric conditions.
  • Opioid agonist therapy is the gold standard for heroin addiction treatment.
  • Methadone is a full opioid agonist used for opioid agonist therapy in opioid treatment programs.
  • Methadone maintenance programs typically start with a dose of ≤30 mg and adjust to the lowest effective dose that suppresses withdrawal signs and symptoms. Typical dosage is between 60 mg and 120 mg QD.
  • Adverse effects include constipation, weight gain, drowsiness, excessive sweating, and changes in libido. Risk of overdose (accidental or deliberate).
  • Can increase QT interval, precipitating torsade de pointes and other arrhythmias. Should be avoided in patients with baseline prolonged QTc; use with caution if coadministering other medications that prolong QT.
  • Methadone levels may be lowered by various ARVs; see Table 1, and Common Medications.
  • Buprenorphine is a partial mu-opioid agonist and weak kappa antagonist with 25-50 times the analgesic potency of morphine. It has a pharmacologic "ceiling," and a lower risk of overdose and abuse than full opioid agonists.
  • By federal regulation and VHA policy; physicians are able to prescribe buprenorphine only with 8 hours or more of special training and a specific DEA certificate. See PBM Criteria for Use.
  • It is administered sublingually, in tablet or film formulation.
  • At high dosages, it may block the effects of full opioid agonists, leading to withdrawal. Therefore, patients should stop taking short-acting opioids 12-24 hours before starting buprenorphine and reduce their methadone use to a maximum of 30-40 mg/day.
  • In the United States, buprenorphine is most commonly coformulated with naloxone. Naloxone is poorly absorbed sublingually; however, if the tablet is crushed and injected parenterally, the naloxone precipitates opiate withdrawal.
  • Buprenorphine has been approved for use in office-based opioid dependence treatment outside regulated Opioid Treatment Programs. See Table P2 for patient suitability considerations.
  • Buprenorphine is induced with an initial daily dosage of 2-8 mg and is increased by 2-4 mg QD until relief from withdrawal symptoms is achieved. The usual dosage is 12-16 mg QD; maximum recommended dosage is 32 mg QD.
  • Side effects include depression, disturbed sleep, drowsiness, sweating, headaches, nausea, constipation, and reduced libido. Mild increases in ALT have been reported. Respiratory depression may occur, especially if misused intravenously.
  • Buprenorphine may interact with PIs and with EFV; see Table 1.
  • In acute pain episodes, buprenorphine can be used Q8H for analgesic effects.
  • Naltrexone: opioid antagonist. Precipitates opiate withdrawal; appropriate only for patients with >7 days of abstinence.
  • May be a useful adjuvant to psychosocial therapy (though data are limited).
  • Compliance has been poor with the oral tablets; an extended-release formulation has better compliance and is FDA approved but does not yet have Pharmacy Benefits criteria for use in VHA.
  • Consider oral naltrexone as a component of a substance abuse program for highly motivated patients (eg, those who face severe consequences for relapse, such as health care professionals and parolees).
Behavioral Interventions
  • If unstable (medically or psychiatrically), refer to an emergency department or hospitalize.
  • Behavioral interventions are the mainstay of treatment; no pharmacologic agents have proven efficacy.
  • Refer to outpatient or inpatient behavioral counseling: including motivational interviewing and cognitive-based therapy (eg, Matrix Model), contingency management to reward early abstinence.
  • Refer to harm reduction programs.
  • For local (non-VA) substance abuse resources: 800-662-HELP.
  • Narcotics AnonymousLink will take you outside the VA website. VA is not responsible for the content of the linked site. provides methamphetamine-specific groups.
  • Crystal Meth AnonymousLink will take you outside the VA website. VA is not responsible for the content of the linked site..
  • Ask about ART adherence at each visit, as methamphetamine users frequently go on binges that lead to interruptions in ART adherence.
  • Methamphetamine use is associated with unsafe sexual behaviors. Explore risk behaviors, screen for STDs, and counsel on safer sex options; see Prevention for Positives.
  • Provide written or illustrated instructions that can be processed visually, as methamphetamine users often have impaired auditory memory.
Pharmacologic Interventions
  • For treatment of acute methamphetamine withdrawal, no medication has proven to be effective.
  • Treat comorbid psychiatric conditions.
  • Antidepressants have not been shown to improve long-term treatment outcomes.
  • Dextroamphetamine "replacement therapy" has not shown greater efficacy than placebo. Studies of other treatments are ongoing.
  • Many patients who quit do so because they tire of the chaotic lifestyle associated with chronic methamphetamine use.
  • RTV inhibits amphetamine metabolism and can lead to a 2- to 3-fold increase in amphetamine levels. Patients should be educated about this interaction.
Behavioral Interventions
  • Refer to cognitive-behavioral therapy tailored to substance abusers.
  • For local substance abuse resources: 800-662-HELP.
  • Narcotics AnonymousLink will take you outside the VA website. VA is not responsible for the content of the linked site. also provides cocaine-specific groups.
Pharmacologic Interventions
  • No medication has been FDA approved for the treatment of cocaine addiction. Systematic reviews of antidepressants, dopamine agonists, anticonvulsants, and antipsychotics have not shown consistent efficacy.
  • Treat comorbid psychiatric conditions.
  • Disulfiram, topiramate, tiagabine, and modafinil are currently being studied for prevention of relapse.
  • Peer support groups such as Cocaine Anonymous can improve outcomes.
Club drugs (see below)
Behavioral Interventions
  • Refer to cognitive-behavioral therapy tailored to substance abusers.
  • For local substance abuse resources: 800-662-HELP.
  • Narcotics AnonymousLink will take you outside the VA website. VA is not responsible for the content of the linked site. also provides group support for club drug users.
Pharmacologic Interventions
  • Treat comorbid psychiatric conditions.
  • RTV increases MDMA levels 5- to 10-fold and can increase the risk of fatal heatstroke and dehydration.
  • RTV also increases GHB levels, leading to increased risk of seizures, respiratory depression, and loss of consciousness.
Table 1. Potential ARV Interactions

(Print table)


  • The following may ↓ methadone levels. Monitor for signs of opiate withdrawal. Dosage adjustment of methadone may be needed.
    • NRTIs: ABC
    • PIs: ATV, DRV, FPV/r, LPV/r, NFV, SQV/r, TPV/r
  • DLV may ↑ methadone levels. Start methadone at low dosage, monitor for methadone toxicity.
  • Methadone may ↓ ddI levels. Dosage adjustment not established.


  • PIs: May ↑ buprenorphine levels and ↑ risk of adverse effects.
  • EFV: May ↓ buprenorphine levels; monitor for signs of opiate withdrawal.
  • Dosage adjustment of buprenorphine may be needed; monitor for signs of buprenorphine intoxication or withdrawal, and titrate as needed.


  • PIs: May ↑ and prolong ketamine effects (↑ sedation, ↑ heart rate and blood pressure)

Cannabis/marijuana, ecstasy/MDMA, amphetamines benzodiazepines, GHB: PIs may ↑ these drug levels; patients should be warned of potential increased risk of toxicity and avoid or reduce doses.

Cannabis and Club Drugs

The effects of club drugs are less well-characterized. Here is an overview of the effects of cannabis and some common club drugs:

Illicit DrugEffectsNotes
Cannabis (marijuana)

Also known as chronic, pot, weed, grass, Mary Jane, spliff, ganja, hash, skunk, puff, herb, and many other names
Intoxicant, stimulant, psychedelic (mild hallucinogenic), relaxant Both physical and psychological dependence are possible. A chronic heavy user can appear apathetic and unmotivated, and may perform poorly at work or school.

Other health risks include those associated with impaired judgment and coordination, increased incidence of respiratory infections, as well as toxicities from adulterants (eg, formaldehyde).

Note: Programs that authorize medical use of marijuana exist in a number of states and the District of Columbia, and VHA patients may access these programs through non-VHA providers. For patients who do participate in a marijuana program, VA providers should assess for misuse, adverse effects, and withdrawal. Participation in state-approved marijuana programs cannot in itself be a cause for denial of access to most VA clinical programs.


Also known as ecstasy, E, X, XTC, rolls, beans, Adam

Stimulant, hallucinogenic amphetamine

MDMA is one of the most popular recreational psychoactive drugs, most commonly sold in the form of "ecstasy" tablets. It is known for its empathogenic, euphoric, and stimulant effects.

Physical effects are similar to those of amphetamines.

Between 300 and 400 deaths have been reported from MDMA use and overheating.

Concurrent use with amphetamines, cocaine, or alcohol increases the risk of overheating.

RTV increases MDMA levels 5- to 10-fold and can increase the risk of fatal heatstroke and dehydration.

Flunitrazepam (Rohypnol)

Also known as roofies, "date-rape" drug

Benzodiazepine sedative-hypnotic

Flunitrazepam has been used in many "date rapes" in the United States, with cases also reported in Europe and Australia.

10 times more potent in sedative-hypnotic effects than diazepam.

Causes paralysis, unconsciousness, and short-term amnesia.

Onset occurs within 10 minutes after being taken; the effects peak in 8 hours and last 12 hours.

Mixing with alcohol at higher doses can lead to unconsciousness for several days.

Gamma-hydroxybutyrate (GHB)

Also known as liquid ecstasy, GBL (a pro-drug), BDO, GBH, Blue Nitro, Midnight Blue, RenewTrient, Reviarent, SomatoPro, Serenity, Enliven

Sedative depressant, anesthetic

GHB is popular on the rave scene. It has effects of alcohol-like intoxication and sexual disinhibition.

Higher doses can lead to disorientation, blurred vision, nausea, vomiting, impaired physical coordination, and muscle spasms.

Onset occurs within minutes; overdose can lead to unconsciousness within 30 minutes. The risk of coma and death is potentiated by concurrent alcohol use.

RTV increases GHB levels, leading to increased risk of seizures, respiratory depression, and loss of consciousness.

Ketamine hydrochloride

Also known as K, Special K, Dorothy, cat tranquilizer, tekno, green

Dissociative anesthetic, hallucinogenic (same class as phencyclidine, or PCP)

Ketamine was developed as a veterinary and human anesthetic, but it has become popular in club and rave scenes.

Initial effects are of stimulation and euphoria, followed by sedation and hallucination (out-of-body sensations). Physical effects include nausea and vomiting, slurred speech, lack of coordination, and numbness.

Physical risks include injury resulting from the anesthetic effects. Overdoses can lead to respiratory compromise.

Used chronically, ketamine can increase the risk of drug-induced hepatitis.

Print table

Pain Management in Patients with an SUD

Pain management should be in accordance with the principles of the VHA?s stepped care model for management of pain across the continuum of care, from acute to chronic.

  • The prevalence of self-reported pain among HIV-infected patients ranges from 28-97%.
  • HIV-infected patients with an SUD are more likely to be untreated or undertreated for pain.
  • Pain management in SUD patients may be complicated by opiate tolerance.
  • Clinician concerns about pain management in patients with an SUD include:
    • Drug seeking by patients
    • Diversion
    • Relapse to substance abuse
    • Legal repercussions
    • Inadequate knowledge or skills on the part of the clinician
    • Unavailability of specialists
  • SUD patient concerns about pain management include:
    • Relapse to substance abuse
    • Anticipated physical discomforts (eg, thinking that medicines will be injected; fearing side effects)
    • Fearing accusations of malingering
    • Perceived "weakness" in taking medications for pain
  • Appropriate evaluation of pain in the HIV-infected SUD patient includes:
    • An accurate and complete pain history, including results of previous evaluations; distinguishing between neuropathic and nonneuropathic pain may help guide therapy
    • Use of a numeric pain scale to assess and follow severity and response to therapy
    • Appropriate and complete evaluation to identify correctable causes of pain (eg, use of a neurotoxic medication in a patient complaining of painful neuropathy)
    • Accurate and complete documentation of findings via CPRS
  • Principles of pain management in the HIV-infected SUD patient include:
    • Having a single provider prescribe all pain medications
    • Accurate and complete documentation of the rationale for the treatment used, including dosage, dose interval, amount prescribed, and refill procedures
    • If a patient has an active SUD, consultation with or referral to a treatment program
    • Agreement with the patient on goals of therapy:
      • In cases of acute pain, elimination of pain is a reasonable goal, with agreement on when the need for therapy will end
      • For chronic pain, the goal should be reasonable relief of pain with a maximum level of functioning
    • Use of specific rules ("contract") that addresses reports of lost medications, missed appointments etc, to promote accountability and decrease the risk of diversion or drug-seeking behavior.
    • Pretreatment agreement to random urine toxicology screens
    • Use of a stepwise approach to analgesia (see Pain Medications)
    • Use of nonpsychotropic pain medications, when possible, to achieve pain relief
    • When opiates are indicated, use the minimum dosage needed to relieve pain
    • Around-the-clock dosing is more effective than use as needed
    • Ensuring that adequate pain relief is obtained to prevent self-medication: Increasing dosages may be required if the underlying cause of pain (eg, malignancy) progresses or tolerance develops
    • Referral to a pain specialist for complex management issues or concerns over drug-seeking behavior