Kevin P. Hill, MD, MHS

Special Report Chairperson: Tony P. George, MD, FRCPC

In the United States, cannabis is a Schedule I drug. However, legislative matters have effectively allowed each state to manage legalized recreational cannabis. This patchwork has led to disparities in state versus federal regulations regarding recreational 

 that, coupled with myths about its psychological benefits, increase confusion for our patients. This article will summarize changes in cannabis legislation and provide an update for psychiatrists on the evidence both for and against its clinical utility.

Recovery-Based Approaches and Forward-Thinking Policy: Implications for Addiction Care

Ashley E. Kivlichan; Darby J.E. Lowe, MSc; Tony P. George, MD, FRCPC

Nonabstinent Recovery From Alcohol Use Disorder

Cassandra L. Boness, PhD; Alena Kuhlemeier, PhD; Katie Witkiewitz, PhD

Dual Diagnosis: Double the Stigma, Double the Trouble

Darby J.E. Lowe, MSc; Emily Simpkin, RN; Tony P. George, MD, FRCPC

Eighteen states (and Washington, DC, and Guam) have adopted legalized recreational cannabis use, and 37 (plus DC, Guam, Puerto Rico, and the US Virgin Islands) have approved medicinal use. While this patchwork leads to disparities in medical care and arrests across states, it allows for comparisons in mental health trends related to legalization. Longitudinal analysis of 505,796 respondents found an increased diagnosis of cannabis use disorder (CUD) in individuals aged 12 to 17 years (2.2% to 2.7%) and 26 years and over (0.9% to 1.2%) after legalization, which was not mirrored in states where it remains illegal.

 However, there was no increase in CUD prevalence for respondents aged 18 to 25 years.

Evidently, for consumers to make informed choices and to reduce potential harms, legalization alone may be risky and should be coupled with increases in evidence-based education and access to treatment, especially for at-risk groups such as adolescents and individuals with mental illnesses.

CUD refers to continuous excessive use, characterized by a loss of control, psychological and social impairments, and risky behavior. The prevalence of CUD (ages 12+) is around 2.9% in the United States,

 with males having rates twice that of than females.

 However, in psychiatric patient samples, CUD prevalence reaches ~25%.

 Individuals with mental illnesses and other SUDs may be more susceptible to CUD because of shared genetic and environmental factors increasing vulnerability,

 or because of overuse in an effort to manage symptoms (ie, coping with negative affect).

 There is the popular perception that cannabis is an effective tool in managing anxiety, mood, and eating disorders, but evidence to support self-medication is minimal.

 in cannabis are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is known to produce the characteristic “high” from inhalation of cannabis because of its high-affinity for cannabinoid type 1 (CB1) receptors in the mesolimbic dopamine system; CBD antagonizes these effects, but the exact mechanism is unclear.

The acute effects of THC intoxication, including at higher doses, are outlined in the 

. Cannabis misuse is associated with first-episode psychosis, longer psychotic episodes, more positive symptoms, and poorer psychosocial functioning in individuals with schizophrenia.

 Such effects directly correlate with THC dose and potency; evidence suggests a dose-dependent relationship between cannabis use and schizophrenia that cannot be explained by use of other psychoactive substances.

 Similarly, in bipolar disorder, cannabis use is associated with earlier onset of depressive, manic, and psychotic episodes and more frequent suicide attempts,

 with high THC as the culprit. Moreover, longitudinal studies on bipolar disorder show lower rates of treatment adherence and greater symptom severity, particularly mania and psychosis, in bipolar cannabis users.

Less clear is the interaction between THC and depression. While cannabis prevalence in depression is high,

 longitudinal studies have provided modest evidence on whether 

 Infrequent use may not be related to depression, whereas heavy use is more likely to increase symptoms.

 Similarly, evidence on cannabis as a risk factor for anxiety disorders is modest, with some prospective studies showing greater risk of developing anxiety disorders and more anxious symptoms in cannabis users,

 while others have failed to replicate such findings.

 These inconsistencies might be explained by genetic differences

 or the dose-dependent nature of THC intoxication, with low doses eliciting feelings of relaxation and euphoria, while higher doses result in dysphoria, panic, and paranoia. Moreover, extensive exposure to THC over time may paradoxically increase anxiety via changes in allostatic load.

 Despite claims that cannabis helps reduce depression and anxiety, we found no controlled clinical trials suggesting its effectiveness. In fact, in a recent study of 28 days of cannabis abstinence in people with 

, there was a significant improvement in depressive and anxiety symptoms, sleep problems, and anhedonia with extended cannabis abstinence, which argues against self-medication of mood symptoms by cannabis use.

 Conversely, CBD does not produce intoxication. Rather, it has been shown to antagonize CB1 and CB2 receptors, thus opposing effects of THC. Preclinical models suggest a range of potential therapeutic benefits of CBD as a function of antipsychotic, neuroprotective, anxiolytic, and sedating properties.

 For example, animal models suggest that 

 might produce antidepressant effects via serotonergic neurotransmission, in particular activation of 5-HT1A receptors.

Preliminary evidence in human studies is similarly encouraging: CBD may produce antianxiety and antidepressant effects.

 Interestingly, increased doses are not associated with dysphoria or anxiety as is found with increased THC doses. One study found that administration of CBD produced functional changes in anxiety-related limbic and paralimbic cortical areas that were further associated with a reduction in state anxiety.

 Moreover, there is evidence that CBD 200 to 1500 mg daily may alleviate psychotic symptoms through inhibition of anandamide metabolism and reduce cognitive impairments through CB1 and CB2 receptor agonism in schizophrenia.

One case study even found improvements in symptoms of 

where the individual had previously failed to respond to olanzapine, clozapine, or haloperidol.

 Even where findings are null, CBD is well tolerated and does not worsen symptoms.

 Thus, emerging evidence on anxiolytic, antipsychotic, and antidepressive effects of CBD is promising. Of note, there are a number of drug interactions between CBD and common psychiatric medications that need to be considered when prescribing CBD.

In addition, some studies have found support for the use of CBD in treating cannabis-related issues. Specifically, CBD at 40 to 100 mg daily has been shown to improve cannabis withdrawal symptoms,

 which may help participants avoid using to alleviate withdrawal. Other open-label studies have found that CBD increased rates of abstinence and reduced the amount of cannabis used by participants.

Unfortunately, trends observed in concentrations of THC and CBD in cannabis in licit and illicit markets have seen the former increasing from an average of 4% to as high as 25% to 30%, and the latter decreasing from 0.28% to less than 0.15% (1995-2014).

 This imbalance precludes the opposing effects of CBD on THC intoxication, increasing the risk of experiencing harms associated with 

Cannabis Legalization and the Opioid Toxicity Crisis

The rapidly increasing rates of opioid-related poisonings has galvanized health care providers, advocates, and governments to find solutions to overprescription of 

 and the toxicity of the illicit opioid market (eg, carfentanil). It has been proposed that legalization of cannabis may play a role in curbing the opioid crisis.

A few studies have attempted to answer this question. Initially, Bachhuber et al

 suggested that in states with medical cannabis laws, rates of fatal opioid overdoses were reduced after implementation of these laws. However, more recent studies have suggested the opposite

 and that frequency of cannabis use, in fact, correlates with the severity of opioid use disorder.

 These studies, although methodologically sound, are not entirely sufficient to answer the question of whether cannabis legalization may curb the opioid crisis—a broad and somewhat vague claim. Examining a few scenarios will help highlight the importance of defining the potential role of cannabis legalization in reducing opioid overdoses.

, prescription of high-dose opioids long term may increase the risk of developing opioid use disorder

 that may in turn result in transition to use of illicit opioids (eg, heroin, fentanyl).

 In these cases, prescribing cannabis for pain management may, in fact, reduce the chances of introduction to and dependency on opioids.

It has also been suggested that recreational cannabis use may act as a “gateway drug” that encourages transition to use of other drugs, such as opioids. In states where cannabis remains illegal, 1 potential mechanism of this transition (if it occurs) is introduction to the illicit market, criminal networks, and potentially the judicial system if one were arrested. In this instance, legalization of cannabis means individuals could access regulated amounts without having to go through illicit sources.

However, for individuals who already have an 

 that has arisen from a complex array of biological, psychological, and social circumstances, legalization of cannabis may not affect their use of opioids. Rather, as suggested by Olfson et al,

 we may see that individuals continue to use opioids alone or with cannabis and thus would likely benefit more from a specific and targeted opioid use disorder intervention.

As such, well-controlled longitudinal studies are needed to adequately investigate the clinical and public health relationships between cannabis use and opioid toxicity.

While there remains a dearth of clinical research on the benefits of cannabis, particularly in individuals with mental illnesses, the evidence suggests they are likely outweighed by the harms of (high-THC) cannabis. However, the question is no longer should cannabis be legalized? The question is how can we effectively promote evidence-based public health messaging around cannabis, regulate available supplies to achieve an appropriate balance of THC and CBD, and increase access to CUD treatment?

is a research analyst at the Centre for Addiction and Mental Health (CAMH), Toronto, Ontario, Canada. 

 is an associate professor of psychiatry at Harvard Medical School, and director of addiction psychiatry at Beth Israel Deaconess Medical Center (BIDMC) in Boston, Massachusetts.

is professor of psychiatry, Temerty Faculty of Medicine, at the University of Toronto, and senior physician-scientist at CAMH in Toronto, Ontario, Canada. He is currently deputy editor and incoming coprincipal editor of Neuropsychopharmacology (NPP).

Acknowledgements: This work was funded in part by NIH grant R21-DA-043949 to Dr George.

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Association between recreational marijuana legalization in the United States and changes in marijuana use and cannabis use disorder from 2008 to 2016.

US epidemiology of cannabis use and associated problems.

A systematic review and meta-analysis of sex differences in cannabis use disorder amongst people with comorbid mental illness.

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Diversity of molecular targets and signaling pathways for CBD.

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Does cannabis use affect treatment outcome in bipolar disorder? A longitudinal analysis.

Association of cannabis use in adolescence and risk of depression, anxiety, and suicidality in young adulthood: a systematic review and meta-analysis.

 Exploring the association between cannabis use and depression.

11. Otten R, Huizink AC, Monshouwer K, et al. 

Cannabis use and symptoms of anxiety in adolescence and the moderating effect of the serotonin transporter gene.

12. Lucatch A, Kloiber S, Meyer J, et al. Effects of extended cannabis abstinence in major depressive disorder. 

The therapeutic role of cannabidiol in mental health: a systematic review.

14. Silote GP, Sartim A, Sales A, et al. 

Emerging evidence for the antidepressant effect of cannabidiol and the underlying molecular mechanisms.

15. Zieba J, Sinclair D, Sebree T, et al. 

Cannabidiol (CBD) reduces anxiety-related behavior in mice via an FMRP-independent mechanism.

16. Crippa JA, Derenusson GN, Ferrari TB, et al. 

Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report.

17. Leweke FM, Mueller JK, Lange B, et al. 

Role of the endocannabinoid system in the pathophysiology of schizophrenia: implications for pharmacological intervention.

The effects of cannabidiol (CBD) on cognition and symptoms in outpatients with chronic schizophrenia a randomized placebo controlled trial.

19. Hill KP, Gold MS, Nemeroff CB, et al. 

Risks and benefits of cannabis and cannabinoids in psychiatry.

20. ElSohly MA, Mehmedic Z, Foster S, et al. 

Changes in cannabis potency over the last 2 decades (1995-2014): analysis of current data in the United States.

21. Bachhuber MA, Saloner B, Cunningham CO, Barry CL. 

Medical cannabis laws and opioid analgesic overdose mortality in the United States, 1999-2010.

Association of state policies allowing medical cannabis for opioid use disorder with dispensary marketing for this indication.

23. Olfson M, Wall MM, Liu SM, Blanco C. 

Cannabis use and risk of prescription opioid use disorder in the United States.

24. Hoffman KA, Ponce Terashima J, McCarty D. 

Opioid use disorder and treatment: challenges and opportunities.

25. National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Health Sciences Policy; Phillips JK, Ford MA, Bonnie RJ, et al, eds. 

Pain Management and the Opioid Epidemic: Balancing Societal and Individual Benefits and Risks of Prescription Opioid Use.

 National Academies Press (US); 2017. ❒

Articles

What's the latest update on cannabis legislation and its clinical utility?

Cannabis Legalization: What Psychiatrists Need to Know

For information on treatment of amphetamine related disorders, please refer to the articles at the end of this case.This case vignette illustrates some common features of patients presenting with methamphetamine dependence. Comorbidities are often present, with psychiatric comorbidites prominent throughout the addiction, and physical problems developing with persistent methamphetamine use.Although valiant efforts have been made to reduce access to the chemical precursors of methamphetamine, it is likely that methamphetamine use will remain accessible and inexpensive, and costs associated with increased use will continue to rise.This case is based on a Psychiatric Times article, "Treatment for Methamphetamine Dependence," by Kevin P. Hill, MD, MHS. Dr Hill is author of Marijuana: The Unbiased Truth about the World's Most Popular Weed (Hazelden, release date March 31, 2015). Twitter: @DrKevinHill.Also see: Intoxication With Street Drugs

Slideshows

A 28-year-old married mother of 2 with a history of depression is brought to the emergency department after 6 months of near-daily methamphetamine use.

Psychiatric Emergency: Methamphetamine Abuse

In this 4-minute video, addiction psychiatrist, Kevin Hill, MD, talks about the pros and cons of legalization of the recreational use of marijuana.

Incarceration (disproportionate arrests of blacks for marijuana possession that legalization may correct)

Will increased marijuana use lead to increased addiction?

Involvement of Big Tobacco and Big Alcohol

Driving while impaired (no technology to measure level of impairment)

Dr Hill is the author of the soon-to-be published 

Marijuana: The Unbiased Truth About the World's Most Popular Weed.

A brief video on the pros and cons of legalizing the recreational use of marijuana.

Should Recreational Use of Marijuana Be Legalized?

Methamphetamine dependence has grown into an epidemic in the United States. An estimated 10.4 million people aged 12 years or older have tried methamphetamine.

 While the prevalence of methamphetamine use has remained constant in recent years, severity of use is increasing. The number of methamphetamine users in the past month meeting criteria for amphetamine abuse or dependence during the past year has more than doubled from 27.5% in 2002 to 59.3% in 2004.

 In 2004, 4% of all drug-related visits to the emergency department (ED) were because of methamphetamine abuse.

 In 2006, there were an estimated 761,000 current users of methamphetamine aged 12 years or older.

 Although valiant efforts have been made to reduce access to the chemical precursors of methamphetamine, it is likely that methamphetamine will remain accessible and inexpensive, and costs associated with increased use will continue to rise.

Significant public health effects resulting from methamphetamine use underscore the need for effective treatment. Synthesis of methamphetamine in homemade laboratories has resulted in environmental costs, increased pediatric deaths from and ED visits for burns and poisoning, and prenatal complications from in utero exposure.

 Higher rates of hepatitis C and HIV infection have also been reported.

 As a result, a great deal of work has been done to develop effective treatments for methamphetamine dependence.

Unfortunately, there are still few effective tools for clinicians to use in treating methamphetamine dependence. Pharmacotherapy trials have yielded inconsistent results thus far, while trials of behavioral therapies have provided promising results requiring further development. In this review, we summarize current knowledge from studies about treatments for methamphetamine dependence and introduce techniques to help uncover new treatment targets.

Several potential therapeutic targets for the treatment of amphetamine dependence have been identified in studies of preclinical models of addiction.

 Medications acting on dopamine, g-aminobutyric acid (GABA), glutamate, cannabinoid, nicotinic, and opioid receptors have produced findings warranting further study, but the resulting clinical studies have yet to produce reliable treatments.

The positive findings seen in preclinical studies have not, for the most part, been reproduced in humans. Randomized controlled trials (

) and open-label studies of several classes of medications have generated inconclusive results. However, positive findings, although seen in only a few of these trials, provide hope for the eventual identification of a medication for methamphetamine dependence.

Antidepressants, including SSRIs and tricyclic antidepressants (TCAs), have been studied as potential treatments for methamphetamine dependence for 2 important reasons. First, serotonergic medications may attenuate the reinforcing effects of methamphetamine based on preclinical studies demonstrating the role of serotonergic neurons in amphetamine self-administration.

 Second, blockade of seroto- nergic and noradrenergic reuptake may alleviate the depressive methamphetamine withdrawal symptoms that can lead to relapse.

Trials of both SSRIs and TCAs, however, have had limited success. The SSRIs fluoxetine, paroxetine, and sertraline failed to distinguish themselves from placebo in reducing methamphetamine use.

 Imipramine has been shown to improve treatment retention but not urine drug screen results, depression scores, or craving in an outpatient setting.

Other antidepressants have been studied as well. In a promising recent study, Elkashef and colleagues

 showed that bupropion, a dopamine and norepinephrine reuptake inhibitor, may be effective as a treatment for methamphetamine dependence in at least a subgroup of men who are low to moderate users, increasing the number of weeks of methamphetamine-free urine drug screens.

 Amineptine, a dopamine reuptake inhibitor available in Europe that has mild stimulant properties and mirtazapine, a serotonin 5HT

 blocker, have shown promise as treatments for methamphetamine withdrawal symptoms.

GABAergic agents may also be useful in the treatment of methamphetamine dependence. Neither gabapentin, a GABA-transaminase inhibitor, nor baclofen, a GABA

 agonist, produced significant differences relative to placebo on standard treatment outcome measures in a 16-week, randomized, placebo-controlled, double-blind trial.

 Post hoc analyses, how- ever, showed a significant treatment effect for baclofen compared with placebo in a subgroup of patients who took a high percentage of study medication. g-Vinyl-GABA, another GABA-transaminase inhibitor, was shown to be a safe treatment for methamphetamine dependence in an open-label, 9-week safety study.

 Fifteen of 27 methamphetamine-dependent patients completed the study and two thirds or more were drug-free for at least 4 weeks of the study.

Atypical antipsychotics have also been considered as treatments for methamphetamine dependence because of the effects of dopamine and, to a lesser extent, 5HT on amphetamines. Treatment with risperidone, a D

 antagonist, resulted in significant reductions in episodes of methamphet-amine use and psychiatric symptoms in a 4-week, open-label trial.

Preclinical studies demonstrating the ability of calcium channel blockers to suppress the rewarding effects of amphetamines have led to the study of this class of medications in humans. In a double-blind, randomized, placebo-controlled trial, a calcium channel blocker, amlodipine, failed to distinguish itself from placebo on measures of methamphetamine use, depressive symptoms, and craving.

Modafinil, a wakefulness-promoting agent with effects similar to those of amphetamines, was studied in a small open-label trial as a treatment for methamphetamine withdrawal. Treatment with modafinil resulted in decreased subjective and observer-reported withdrawal severity compared with treatment as usual, with the modafinil group reporting less hypersomnia, fewer nighttime awakenings, and deeper sleep than the control group.

Thus far, trials of psychotherapy for methamphetamine dependence have produced better results than trials of pharmacotherapy. Both cognitive-behavioral therapy (CBT) and contingency management have been shown to reduce methamphetamine use. CBT involves examining learning processes in order to reduce methamphet-amine use; a patient benefiting from CBT would become skilled at recognizing situations associated with use, avoiding them when possible, and coping with them when necessary.

Contingency management provides tangible incentives, such as money or prizes, based on objective measures of drug abstinence. Rawson and colleagues

 included CBT as part of the Matrix Model, a 4-month, manualized, intensive outpatient therapy that combines CBT, psychoeducation, a 12-step program, and positive reinforcement for behavioral change and treatment compliance.

 In a multicenter clinical trial of 978 methamphetamine-dependent individuals, it proved more effective as a 16-week treatment for methamphetamine dependence than standard treatments, increasing treatment retention, the number of methamphetamine-free urine drug screens, and periods of abstinence. Although improvements seen using the Matrix Model did not persist at discharge or at 6 months after admission, this important study demonstrated the efficacy of an intensive, multifaceted, structured treatment program for methamphetamine dependence.

Four recent clinical trials point to the promise of contingency management as a treatment for methamphetamine dependence. The results of a study by Shoptaw and colleagues

 showed that contingency management using voucher-based reinforcers improved treatment retention and increased periods of continuous abstinence compared with standard CBT in a 16-week trial of 162 methamphetamine-dependent homosexual and bisexual men--groups hit especially hard by methamphetamine's recent popularity.

 Another study by the same group looked at contingency management in conjunction with CBT and sertraline in methamphetamine-dependent participants; those who received contingency management were significantly more likely than those who did not to achieve 3 weeks of in-treatment abstinence.

In a 12-week study of 415 persons addicted to methamphetamine or cocaine, contingency management outperformed treatment as usual in treatment retention and abstinence in a community treatment setting.

 Similarly, in a 16-week study of 171 individuals dependent on methamphetamine or cocaine, contingency man- agement was shown to be more effective than CBT in treatment retention and abstinence.

 Interestingly, no additive effect was seen with the combination of contingency management and CBT. This study illustrates the use of contingency management in engaging methamphetamine-dependent patients and helping them stay in treatment while achieving abstinence. As with the pharmacotherapy trials, the aforementioned results demonstrate a need for additional randomized clinical trials of psychotherapy .

Ms A, a 28-year-old married mother of 2 with a history of depression, was brought to the ED by her mother for worsening depressive symptoms and passive suicidal ideation in the context of 6 months of near-daily methamphetamine use. She reported drinking 4 or 5 drinks 2 or 3 times a week. She stopped smoking methamphetamine a week ago and had not ventured outside of her home since.

Her mother visited her the day before bringing her in to the ED and was alarmed to find Ms A disheveled, markedly less energetic than usual, anxious with paranoia about the neighbors' interest in her activities, and lamenting her current living situation to the point where she made statements about not wanting to live. Such behavior was out of character for Ms A. She had no history of psychiatric hospitalizations or suicidal ideation. Ms A had stopped taking the antidepressant prescribed 8 months earlier by her primary care physician.

Ms A was seen by the consulting psychiatrist in the ED and, after an unremarkable medical workup she was admitted to the psychiatric unit for safety and stabilization. After a brief hospitalization during which the antidepressant was restarted and an outpatient treatment plan was constructed, she was discharged home. No medication to treat methamphetamine dependence was added.

She began an intensive outpatient program with a dual diagnosis focus that met 3 times a week, with the understanding that she would be referred to a psychiatrist and a therapist at the end of the program for follow-up.

This case vignette illustrates some common features of patients presenting with methamphetamine dependence. Comorbidities are often present, with psychiatric comorbidites prominent throughout the addiction, and physical problems developing with persistent methamphetamine use. Before becoming dependent on methamphetamines, Ms A had a history of depressive symptoms, anxiety, and paranoia.

Treatment teams face the same problems in treating patients with methamphetamine dependence as they do when treating patients with most other addictions. Patients often do not follow up with treatment after hospitalization and, if they do, they often begin a homogenous treatment plan among a heterogeneous population of addiction patients.

The dearth of reliable treatment tools for methamphetamine dependence, especially the lack of effective pharmacotherapy, has led to the development of alternative strategies for the identification of such treatments. Study of the genetics of methamphetamine dependence may determine the level to which individuals are affected by methamphetamine and identify patients for whom a particular treatment may be effective. Work is being done to isolate both risk polymorphisms for experiencing increased effects from methamphetamine and protective polymorphisms in individuals less susceptible to the effects of methamphetamine. The relationship between human gene polymorphisms and associations to amphetamine dependence, response to treatment, and treatment outcome has been reviewed recently.

Pharmacogenetics may be useful in the development of new therapies for methamphetamine dependence by helping to individualize treatments. Pharmacogenetic studies are designed primarily in 2 ways.

 First, new treatment targets, such as particular neurotransmitter systems, could be identified. Second, pharmacogenetic studies could increase the effectiveness of medications currently in use, either by describing subgroups of patients more likely to respond to a given medication or by providing improved dosing recommendations.

With several classes of medications having been investigated as treatments for methamphetamine dependence, it seems unlikely at this point that a single medication will be both effective and safe for most patients. Thus, further work on the development of methods to predict treatment response, using tools such as pharmacogenetic studies, is critical.

Methamphetamine dependence is ravaging many communities in the United States. While increasing numbers of persons addicted to methamphetamine are seeking treatment, clinicians have a limited number of treatment tools at their disposal. Although promising, preclinical studies have had inconsistent results. While there are no established, FDA-approved pharmacotherapies for methamphet-amine dependence, medications such as bupropion, GABAergic agents, and modafinil require additional study in large randomized controlled trials. Fortunately, progress has been made in the development of behavioral treatments for methamphetamine dependence.

The scope of the methamphetamine problem and the complexities of addiction neurobiology make the pursuit of new ideas imperative. Research on pharmacogenetics appears to be a promising new approach that may advance the treatment of amphetamine dependence. Genotypic information may allow clinicians to tailor treatment to each individual by considering polymorphisms that may affect treatment response. New biological treatments and pharmacogenetic information may become integral components of successful treatment plans for amphetamine dependence.

Although recent studies of medications for treatment of methamphetamine use provide hope, there remains a critical need for the identification of effective medications for methamphetamine dependence and further development of the psychotherapies used to treat this disorder.

Dr Hill is a fellow in addiction psychiatry in the department of psychiatry at Massachusetts General Hospital, Boston, and at McLean Hospital in Belmont, Mass. The author reports that he has no conflicts of interest concerning the subject matter of this article.

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