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Objective: The United States is in the midst of rapidly changing laws regarding cannabis. The increasing availability of cannabis for recreational and medical use requires that mental health clinicians be knowledgeable about evidence to be considered when counseling both patients and colleagues. In this review, the authors outline the evidence from randomized double-blind placebo-controlled trials for therapeutic use of cannabinoids for specific medical conditions and the potential side effects associated with acute and chronic cannabis use., Methods: Searches of PubMed and PsycInfo were conducted for articles published through July 2021 reporting on "cannabis" or "cannabinoids" or "medicinal cannabis." Additional articles were identified from the reference lists of published reviews. Articles that did not contain the terms "clinical trial" or "therapy" in the title or abstract were not reviewed. A total of 4,431 articles were screened, and 841 articles that met criteria for inclusion were reviewed by two or more authors., Results: There are currently no psychiatric indications approved by the U.S. Food and Drug Administration (FDA) for cannabinoids, and there is limited evidence supporting the therapeutic use of cannabinoids for treatment of psychiatric disorders. To date, evidence supporting cannabinoid prescription beyond the FDA indications is strongest for the management of pain and spasticity., Conclusions: As cannabinoids become more available, the need for an evidence base adequately evaluating their safety and efficacy is increasingly important. There is considerable evidence that cannabinoids have a potential for harm in vulnerable populations such as adolescents and those with psychotic disorders. The current evidence base is insufficient to support the prescription of cannabinoids for the treatment of psychiatric disorders.

The mainstay of treatment for opioid use disorder (OUD) is opioid agonist therapy (OAT), which modulates opioid receptors to reduce substance craving and use. OAT maintains dependence on opioids but helps reduce overdose and negative sequelae of substance abuse. Despite increasing availability of OAT, its effectiveness is limited by difficulty in initiating and maintaining patients on treatment. With the worsening opioid epidemic in the United States and rising overdose deaths, a more durable and effective treatment for OUD is necessary. This paper reviews novel treatments being investigated for OUD, including neuromodulatory interventions, psychedelic drugs, and other novel approaches. Neuromodulatory interventions can stimulate the addiction neural circuitry involving the dorsolateral prefrontal cortex and deeper mesolimbic structures to curb craving and reduce use, and multiple clinical trials for interventional treatment for OUD are currently conducted. Similarly, psychedelic agents are being investigated for efficacy in OUD specifically. There is a resurgence of interest in psychedelic agents' therapeutic potential, with evidence of improving mood symptoms and decreased substance use even after just one dose. Exact mechanism of their anti-addictive effect is not fully elucidated, but psychedelic agents do not maintain opioid dependence and some may even be helpful in abating symptoms of withdrawal. Other potential approaches for OUD include targeting different parts of the dopamine-dependent addiction pathway, identifying susceptible genes and modulating gene products, as well as utilizing vaccines as immunotherapy to blunt the addictive effects of substances. Much more clinical data are needed to support efficacy and safety of these therapies in OUD, but these proposed novel treatments look beyond the opioid receptor to offer hope for a more durably effective OUD treatment., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Buprenorphine and naloxone (bup/nal), a combination partial mu receptor agonist and low-dose delta mu antagonist, is presently recommended and used to treat opioid-use disorder. However, a literature review revealed a paucity of research involving data from urine drug tests that looked at compliance and abstinence in one sample., Method: Statistical analysis of data from the Comprehensive Analysis of Reported Drugs (CARD) was used to assess compliance and abstinence during treatment in a large cohort of bup/nal patients attending chemical-dependency programs from eastern USA in 2010 and 2011., Results: Part 1: Bup/nal was present in 93.4% of first (n = 1,282; p <.0001) and 92.4% of last (n = 1,268; p <.0001) urine samples. Concomitantly, unreported illicit drugs were present in 47.7% (n = 655, p =.0261) of samples. Patients who were compliant to the bup/nal prescription were more likely than noncompliant patients to be abstinent during treatment (p =.0012; odds ratio = 1.69 with 95% confidence interval (1.210, 2.354). Part 2: An analysis of all samples collected in 2011 revealed a significant improvement in both compliance (p < 2.2 × 10 -16 ) and abstinence (p < 2.2 × 10 -16 ) during treatment. Conclusion/Importance: While significant use of illicit opioids during treatment with bup/nal is present, improvements in abstinence and high compliance during maintenance-assisted therapy programs may ameliorate fears of diversion in comprehensive programs. Expanded clinical datasets, the treatment modality, location, and year of sampling are important covariates, for further studies. The potential for long-term antireward effects from bup/nal use requires consideration in future investigations.

This is the first quantitative analysis of data from urine drug tests for compliance to treatment medications and abstinence from drug abuse across "levels of care" in six eastern states of America. Comprehensive Analysis of Reported Drugs (CARD) data was used in this post-hoc retrospective observational study from 10,570 patients, filtered to include a total of 2,919 patients prescribed at least one treatment medication during 2010 and 2011. The first and last urine samples (5,838 specimens) were analyzed; compliance to treatment medications and abstinence from drugs of abuse supported treatment effectiveness for many. Compared to non-compliant patients, compliant patients were marginally less likely to abuse opioids, cannabinoids, and ethanol during treatment although more likely to abuse benzodiazepines. Almost 17% of the non-abstinent patients used benzodiazepines, 15% used opiates, and 10% used cocaine during treatment. Compliance was significantly higher in residential than in the non-residential treatment facilities. Independent of level of care, 67.2% of the patients (n = 1963; P<.001) had every treatment medication found in both first and last urine specimens (compliance). In addition, 39.2% of the patients (n = 1143; P<.001) had no substance of abuse detected in either the first or last urine samples (abstinence). Moreover, in 2010, 16.9% of the patients (n = 57) were abstinent at first but not at last urine (deteriorating abstinence), the percentage dropped to 13.3% (n = 174) in 2011; this improvement over years was statistically significant. A longitudinal analysis for abstinence and compliance was studied in a randomized subset from 2011, (n = 511) representing 17.5% of the total cohort. A statistically significant upward trend (p = 2.353×10-8) of abstinence rates as well as a similar but stronger trend for compliance ((p = 2.200×10-16) was found. Being cognizant of the trend toward drug urine testing being linked to medical necessity eliminating abusive screening, the interpretation of these valuable results require further intensive investigation.

Over the past three decades, obesity has become a major public health crisis in the United States. The prevalence of obesity in the United States and in other parts of the world has led to a new word, "globesity," being used to describe the problem. As a result of this increased emphasis on understanding the causes and consequences of obesity, novel theories have stimulated new research aimed to prevent, intervene in and ameliorate the effects and decrease the incidence and medical consequences of globesity. One theory that has gained popularity in recent years, is based on the idea that an excessive intake of highly palatable foods shares similarities with the effects on brain and behavior that are seen with some drugs of abuse. Although this theory is not new, empirically-based translational research has only recently provided strong support for this hypothesis. In the present article, we review the present state of the science in this area and describe some newer clinical and preclinical works that shed light on innovative and interesting overlaps between excessivly palatable food intake and drug use., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: NSAIDs used for the treatment of osteoarthritis (OA) have dose-related risks for gastrointestinal, cardiovascular and renal adverse events (AEs), particularly in elderly patients. Topical NSAIDs reduce systemic NSAID exposure and may mitigate these risks., Objective: To evaluate the safety and efficacy of topical diclofenac sodium 1% gel (DSG) versus vehicle in patients aged 25-64 or ≥65 years who have been diagnosed with knee OA., Study Design: Pooled data from three 12-week, randomized, double-blind, parallel-group, multicentre trials., Setting: US primary care, internal medicine, orthopaedic and rheumatology practices., Patients: Aged ≥25 years with mild to moderate (Kellgren-Lawrence grade 1-3) knee OA., Intervention: After a 1-week analgesic washout, patients applied 4 g of DSG or vehicle four times daily to one knee. Rescue paracetamol (acetaminophen) up to 4 g/day was allowed., Main Outcome Measure: Key efficacy outcomes common to the three trials were Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain (0-20) and physical function (0-68) subscales, global rating of disease (GRD; 100-mm visual analogue scale [VAS]) and pain on movement (POM; 100-mm VAS). ANOVA was used to compare efficacy outcome differences (DSG vs vehicle) by age (25-64 or ≥65 years). A flare design was used that defined a subset of patients who experienced increased pain during the washout period (modified efficacy subpopulation [MES])., Results: The MES included both patients aged 25-64 (n = 602) and ≥65 (n = 374) years. Patients in each age group applied >90% of scheduled doses. Among patients aged 25-64 years, the improvement from baseline to week 12 (least squares mean [standard error]) was greater for DSG versus vehicle for WOMAC pain (-5.8 [0.3] vs -4.7 [0.3], p = 0.007), WOMAC physical function (-17.9 [0.9] vs -14.2 [0.9], p = 0.002), GRD (-29.5 [1.6] vs -23.8 [1.6], p = 0.01) and POM (-37.3 [1.8] vs -29.0 [1.8], p < 0.001). Among patients aged ≥65 years, the improvements from baseline for most efficacy outcome scores were significantly greater with DSG versus vehicle: WOMAC pain (-5.3 [0.3] vs -4.1 [0.4], p = 0.02), WOMAC physical function (-15.5 [1.1] vs -11.0 [1.1], p = 0.004) and POM (-33.7 [2.2] vs -26.4 [2.2], p = 0.02). The efficacy of DSG did not differ significantly between patients aged 25-64 years and ≥65 years: WOMAC pain (p = 0.85), WOMAC physical function (p = 0.70), GRD (p = 0.86) and POM (p = 0.81). The incidence of any AE was greater with DSG than with vehicle among patients aged 25-64 years (56.6% vs 50.8%) and ≥65 years (55.8% vs 43.9%). Treatment-related application site dermatitis was more common with DSG compared with vehicle in both younger (4.0% vs 0.7%, respectively) and older (5.8% vs 0.4%, respectively) patients and was the main reason for the difference in treatment-related AEs between the DSG and vehicle groups. Gastrointestinal AEs were infrequent among patients treated with DSG and similar to incidence rates with vehicle in both age groups., Conclusions: DSG was effective and generally well tolerated in adults regardless of age. These data support the topical application of DSG for relief of OA knee pain in elderly and younger patients. Clinicaltrials.gov registration numbers NCT00171626, NCT00171678, NCT00426621.

Background: Obesity, inactivity and being overweight are leading causes of morbidity and mortality in the United States. The relationship between eating, overeating, and addiction have been discussed, debated and more recently investigated. We have hypothesized that drugs of abuse compete with food for brain reward sites. Overeating and obesity may act as protective factors reducing drug reward and addiction., Methods: In the first part of this study, 374 charts of all active weight management patients in a 12-month period were examined. Demographic information, laboratory testing, psychiatric diagnostic interview, alcohol and drug history were reviewed. A detailed alcohol use, abuse, dependence history was present in 298 charts as part of the pre-bariatric evaluation. The relationship between BMI and alcohol use among female patients (n = 298) was then analyzed., Results: We found a significant (p <.05) inverse relationship between BMI and alcohol consumption. The more obese the patient was, the less alcohol they consumed. The percentage of women who consumed alcohol in the past year decreased as BMI level increased. These results confirmed our surgeons' perception that it is rare to find a morbidly obese patient excluded for bariatric surgery because of excessive alcohol consumption., Conclusions: Obese patients have lower rates of alcohol use than found in the general population of women. As BMI increases, lower rates of alcohol consumption are found. Overeating may compete with alcohol for brain reward sites, making alcohol ingestion less reinforcing.

Smoking among teens and college students is a significant public health challenge. Tobacco, marijuana, and alcohol continue to be the most commonly abused drugs by teens and young adults. Educational efforts have resulted in increased awareness of the mortality and morbidity attributed to smoking, second-hand smoke, and prenatal exposure to tobacco. Short- and long-term consequences of marijuana use are well documented in the literature, but they have received less wide spread attention. Even less well known is the relationship between these substances. Does use of one lead to use of the other? Are there synergistic and/or antagonistic effects when these substances are used together? We need answers to these questions to understand the prevalence of use and the impact of these drugs on our nations youth and young adults. The gateway theory of drug use is often used to describe the progression from using alcohol or tobacco, to marijuana, and later use of other drugs like MDMA, cocaine, and heroin. While tobacco use does commonly precede marijuana use, we propose that marijuana may be a "gateway drug" to tobacco smoking. Our research with university students is suggesting that cigarette-smoking initiation often follows or coincides with marijuana.

In this study, a cocaine abstinence syndrome is confirmed. Moreover, the cocaine withdrawal syndrome was found to be medically and psychiatrically benign and required no medication for detoxification in this inpatient setting. The 150 patients who underwent cocaine withdrawal did not show the three distinct phases of the abstinence symptomatology previously described. No patients required pharmacological intervention for cocaine withdrawal, and the dropout rate was 8% of the 150 cocaine dependents. The common symptoms of acute cessation of cocaine were transient craving, hyperactivity, slight tremor, insomnia and apprehension. The diagnosis of cocaine dependence alone without an additional drug or alcohol diagnosis was unusual in this study at 5%, as is the solitary use of cocaine also uncommon according to other studies. Studies clearly document that the concurrent and simultaneous use and dependence on multiple drugs and alcohol is present in the majority of treatment populations and common in the general population. As many as 54% of cocaine dependents qualified for alcohol dependence in this study, and many were dependent on alcohol prior to their cocaine dependence. Cocaine dependence appears to be yet another diagnosis in the spectrum of the multiple drug and alcohol dependent.

Alcohol and drug dependence among the elderly is common and yet frequently underdiagnosed. The practice of self-administration of prescribed medications, particularly sedative/hypnotics, benzodiazepines, and nonprescription, over-the-counter (OTC) medications is prevalent, with untoward consequences in the geriatric population. Dementia, depression, and anxiety syndromes are some of the consequences of alcohol and drug dependence, and may mimic other causes of these disorders. The clinician's index of suspicion must be high enough to make the proper diagnosis of these alcohol- and drug-induced syndromes. Unnecessary evaluations, improper diagnosis, and ineffective and costly treatments may be avoided if alcohol and drug dependence is identified and treated. Effective treatment for alcohol and drug dependence does exist for the elderly and may be instituted in a cost-effective manner.

Multiple drug use occurs in alcoholics in an age-dependent relationship. The younger the onset of alcoholism, the more likely is additional drug use. Drugs used by alcoholics, in decreasing order of frequency, are marijuana, cocaine, and other stimulants, phencyclidine, benzodiazepines, barbiturates, and hallucinogens. Evaluation of intoxication and treatment or detoxification in alcoholics should always include consideration of other drugs. Multiple drug use in alcoholics does not preclude the short- or long-term treatment that traditionally is available for alcoholics, such as programmatic treatment and AA and NA and psychotherapy. The existence of poly-drug addiction in alcoholics and of alcohol dependence in families of drug addicts and alcoholics suggest a common genetic vulnerability to alcoholism and drug addiction.

The potential uses of the laboratory in psychiatric diagnosis and treatment expanded greatly over the decade of the 70s. This paper focuses on some of the newer areas of neurobiological research that may become clinically available to psychiatrists during the decade of the 80s. Research on state markers such as platelet serotonin and MAO levels, CSF metabolites, endorphins, MHPG, TRH and DST is discussed, followed by information on possible trait markers such as HLA gene typing, red blood cell membranes, and beta adrenergic receptor assays. Through these areas of study it is hoped that there will come more accurate psychiatric diagnosis and improved response to treatment.

Although often used in the medical management of anxiety, insomnia, seizures and muscle spasm, benzodiazepines lead to significant complications after continuous use. These complications include tolerance, addiction, dependence and abuse. Knowledge of the diagnostic criteria and treatment of side effects improves the physician's use of these commonly prescribed drugs.

There are clear temporal developmental stages in drug use beginning with cigarettes and alcohol, then progressing to marijuana and finally cocaine, hallucinogens, and other drugs. Of considerable interest is the decline in prevalence of marijuana use and the stabilization of alcohol use in the face of a rise in the incidence of cocaine use. This decline occurs in the face of a decrease in the age of first initiation into drug use. Cocaine use is accompanied by serious medical, psychological, and social consequences including seizures, depression, paranoia, and suspension from school. These findings have definite implications for designing treatment and prevention programs. Inpatient and outpatient programs must require abstinence from drug use. Dysfunctional development, poor interpersonal skills, learning deficits, and concurrent psychiatric illness must be addressed. Family involvement in treatment is mandatory. Every chemically dependent person has a significant impact on the lives of several other people. The social pressures model is the most recent approach to drug prevention and the one most likely to succeed. Direct informational appeals to adolescents are unlikely in themselves to produce immediate changes in drug-related behavior but may assist in gradually changing community norms. School prevention programs need to be designed to target adolescents before the onset of drug use. The seventh grade or before is the correct point to begin. Finally, methods to assess the success of such pilot programs can greatly assist future development efforts. More research into the biologic and behavioral consequences of current drug use patterns including marijuana, cocaine, and hallucinogens is greatly needed.

A structured clinical interview designed to diagnose eating disorders was administered to 259 consecutive callers to the National Cocaine Hotline who met DSM-III criteria for cocaine abuse. Thirty-two percent of those surveyed met DSM-III criteria for either anorexia nervosa, bulimia, or both disorders. The prevalence rates for each of these disorders in this sample appeared elevated even when narrow diagnostic criteria were applied. The data suggest that drug abusers should be screened carefully for the presence of an eating disorder and that abnormalities of eating behaviors seen among these individuals should not be attributed simply to drug use.

A series of research surveys of callers to the "800-COCAINE" National Hotline over the past three years has revealed shifting patterns of cocaine use in the U.S. In addition to showing the geographic spread of cocaine use to virtually all parts of the country, the surveys provide evidence of increased cocaine use among women, adolescents, minorities, and lower socioeconomic groups. Increases have also been seen in individual levels of cocaine consumption, the popularity of freebase smoking, concomitant use of other drugs, cocaine-related automobile accidents, and the use of cocaine in the workplace. Despite inherent limitations, data from the Hotline are highly consistent with large-scale government surveys and predictive of clinical trends.

In the near future the programs, the staff, and the physical plant of private psychiatric hospitals will become increasingly specialized. Development of neuropsychiatric evaluation units and greater liaison between the psychiatric hospital and the clinical laboratory have already begun. Improved standards of patient care and opportunities for research should attract to the private hospital more psychiatrists who are academically oriented. The authors predict a decrease in inpatient acute-care alcoholism treatment and shorter hospital stays for adolescents and those who were formerly considered long-term patients. The private hospital will need to increase its contacts with industry and health maintenance organizations. The authors also predict that ownership will become more centralized in hospital chains, similar to the pattern in general hospitals. The believe the major risk to the private hospital lies in abrupt changes in insurance coverage and regulatory interference.

This paper has demonstrated the persistence of drug abuse as a problem among adolescents and describes cocaine abuse particularly, profiling the typical cocaine abuser. The stagewise progression of drug use has been described. Factors that make youngsters vulnerable to progression to further stages of drug abuse have been suggested. In treatment strategies, the appeal to fear and moral and religious arguments has for the most part necessarily been replaced by an appeal to reason and an educational approach. The coexistence of drug abuse and psychopathology occurs with sufficient frequency to require full medical and psychiatric evaluation in every adolescent who presents with a history of substance misuse. Inpatient and residential treatment, family involvement, and urine monitoring with sufficient aftercare programs seem to be important components of treatment approaches.

1-800 COCAINE has provided assistance to over two million callers to date. It has supplied epidemiologic data regarding cocaine use, with increasing proportions of female users since 1983, decrease in average age and income of callers since 1983, and numerous social and medical consequences of use. In addition, it has provided data regarding timing of the progression of cocaine abuse and confirmation that cocaine abuse is an addictive illness for those calling to seek help. It has corroborated other studies in documenting the psychosocial and medical consequences of addiction and has been a source of insight into trends in cocaine addiction. 800-COCAINE is, by its existence and name recognition, a primary prevention project.