Used appropriately, sedative–hypnotics improve the quality of life for the vast majority of patients who take them. Adverse consequences of their use may include unrecognized memory impairment, physiological dependence, and substance disorders of abuse or dependence. In the elderly, sedative–hypnotics may increase the risk of falls and confusion. Short-acting barbiturates and the older sedative–hypnotics can be lethal if taken in overdose. Benzodiazepines and the newer nonbenzodiazepine hypnotics have a greater margin of safety profile with regard to overdose. The benzodiazepines and newer hypnotics are commonly used by drug abusers, but are rarely used as primary intoxicants. Abuse and dependence and physiological dependence may occur. This chapter focuses on abuse potential, diagnosis of dependence and treatment of benzodiazepine and other sedative–hypnotic drug dependence. Newer nonbenzodiazepine hypnotics—zolpidem, zaleplon, eszopiclone, and zopiclone—are covered in detail because they are now the most commonly prescribed hypnotics, and the manifestations of abuse and dependence and the pharmacotherapy of dependence are less well known. Emphasis is placed on the more recent literature and reviews. Management of physiological dependence is covered in detail. The clinical and biological rationale for using phenobarbital for treatment of physical dependence on sedative–hypnotics is developed, and phenobarbital withdrawal conversions are provided for common benzodiazepines and other sedative–hypnotics. Common issues that arise during evaluation and treatment of sedative–hypnotic dependence are illustrated with case vignettes.

In 1965, I was training in clinical toxicology in the pharmacology department of the University of California San Francisco (UCSF) and living in the Haight Ashbury. I studied various psychedelics, including LSD, mescaline, and ibogaine, in human and animal models. The psychedelics were then being used as a therapeutic drug in clinical settings and researched as a potential antipersonnel agent by the U.S. government. Then, using psychedelics became a rite of passage for the emerging countercultural movement. After adverse reactions and negative publicity, states began to criminalize these drugs, beginning in 1966. The federal government eventually moved these drugs to Schedule 1 classification, shutting down research almost entirely.

A review of the primary role that this journal (and by extension, Dr. David Smith) has played in bearing witness to the second wave of psychedelic research as our modern-day culture embraces the current third wave of the psychedelic revival, exploring through research its therapeutic uses.

The medicalization of the current opioid epidemic in the era of health care reform and parity, and its possible dismantling, poses many challenges. Between 2002 and 2013, drug overdose rates quadrupled. Parallel to an increase in prescription opioid overdose, heroin overdose deaths are increasing as patients shift to cheaper and more accessible heroin from the prescription opioids which physicians are prescribing less often due to increasing regulatory restrictions, as well as enhanced education and awareness. In many areas, the leading cause of death for young adults is drug overdose. Unlike previous heroin use in the U.S., the nexus of spread is coming primarily out of the medical system, as the line between legal and illicit narcotics has become blurred. The economic and social benefits of bringing the previously excluded addicted population into the mainstream health care system will be substantial and will bring changes in three major areas: mental health and substance abuse services in health plans; parity protection in all insurance plans; substance abuse and mental health services. Long-term implementation of these changes in a medically oriented system will require the development of many new systems and procedures.

AIMTo evaluate a calcium activated potassium channel (KCa3.1) inhibitor attenuates liver disease in models of non-alcoholic fatty liver disease (NAFLD).METHODSWe have performed a series of in vitro and in vivo studies using the KCa3.1 channel inhibitor, Senicapoc. Efficacy studies of Senicapoc were conducted in toxin-, thioacetamide (TAA) and high fat diet (HFD)induced models of liver fibrosis in rats. Efficacy and pharmacodynamic effects of Senicapoc was determined through biomarkers of apoptosis, inflammation, steatosis and fibrosis.RESULTSUpregulation of KCa3.1 expression was recorded in TAA-induced and high fat diet-induced liver disease. Treatment with Senicapoc decreased palmitic aciddriven HepG2 cell death. (P < 0.05 vs control) supporting the finding that Senicapoc reduces lipiddriven apoptosis in HepG2 cell cultures. In animals fed a HFD for 6 wk, co-treatment with Senicapoc, (1) reduced non-alcoholic fatty liver disease (NAFLD) activity score (NAS) (0-8 scale), (2) decreased steatosis and (3) decreased hepatic lipid content (Oil Red O, P < 0.05 vs vehicle). Randomization of TAA animals and HFD fed animals to Senicapoc was associated with a decrease in liver fibrosis as evidenced by hydroxyproline and Masson's trichrome staining (P < 0.05 vs vehicle). These results demonstrated that Senicapoc mitigates both steatosis and fibrosis in liver fibrosis models.CONCLUSIONThese data suggest that Senicapoc interrupts more than one node in progressive fatty liver disease by its anti-steatotic and anti-fibrotic activities, serving as a double-edged therapeutic sword.

As of September 2015, the cultivation, possession, and/or use of marijuana is illegal under U.S. federal law as a Schedule I narcotic; however, it is legal in four states and Washington, D.C. Forty-six states allow some form of medicinal marijuana or decriminalization. Marijuana has been used medicinally for thousands of years; Marijuana's regulation by law enforcement in the U.S., rather than the medical community, led to an almost complete halt to academic and scientific research after the 1930s. The late 1960s saw an upsurge in recreational marijuana use by middle-class youth, the majority of whom experienced minimal adverse effects aside from arrest and attendant legal complications. Since the mid-1990s, the use of medicinal marijuana for certain conditions has gained increasing acceptance. Stronger strains and formulations of marijuana pose a risk to the developing brains of adolescents. Within the addiction medicine community, there is currently no consensus on marijuana. In the East, the feeling is primarily that marijuana continue to be proscribed. In the West, where clinicians must face the realities of medicalization, decriminalization, and/or legalization, as well as widespread recreational use, there is more of a movement to minimize adverse effects, particularly on youth.

Since the discovery of its psychedelic properties in 1943, lysergic acid diethylamide (LSD) has been explored by psychiatric/therapeutic researchers, military/intelligence agencies, and a significant portion of the general population. Promising early research was halted by LSD's placement as a Schedule I drug in the early 1970s. The U.S. Army and CIA dropped their research after finding it unreliable for their purposes. NSDUH estimates that more than 22 million (9.1% of the population) have used LSD at least once in their lives. Recently, researchers have been investigating the therapeutic use of LSD and other psychedelics for end-of-life anxiety, post-traumatic stress disorder (PTSD), cancer, and addiction treatment. Adverse psychedelic reactions can be managed using talkdown techniques developed and in use since the 1960s.

Invaluable clinical and treatment information on the most powerful mind-altering drugs in use today. Compiled by two leading professionals from the renowned Haight Ashbury Clinic, the information is based on national and international studies undertaken at the clinic, as well as from 600,000 patient visits, a thorough review of practice and background as reported in the literature, and from their own private practices. An up-to-date reference source, this important guide includes information on the trademark, generic, and popular names of drugs; the use and abuse of drugs; and their acute and chronic effects. An innovative index and cross reference system provide quick, easy access for the physician who must act quickly in an emergency.

(1971). Drug Abuse in Combat: The Crisis of Drugs and Addiction Among American Troops in Vietnam. Journal of Psychedelic Drugs: Vol. 4, The Contemporary Heroin Scene, Part I: The Problem, pp. 23-30.

Abstract Addiction is a primary, chronic disease involving brain reward, motivation, memory and related circuitry; it can lead to relapse, progressive development, and the potential for fatality if not treated. While pathological use of alcohol and, more recently, psychoactive substances have been accepted as addictive diseases, developing brain science has set the stage for inclusion of the process addictions, including food, sex, shopping and gambling problems, in a broader definition of addiction as set forth by the American Society of Addiction Medicine in 2011.

Prescription drug abuse is increasingly recognized as the United States' fastest growing drug problem, rising dramatically since the early 2000s, and particularly affecting adolescents and young adults. Federal officials are urging legislation to educate physicians about the use and effects of potent narcotics, which are increasingly being prescribed for chronic pain. ASAM developed strategies in the 1980s to identify the small minority of misprescribers and focused educational and retraining efforts on these individuals. As health reform and more prevalent pain management put more primary care physicians in a gatekeeper role to manage the medical care of addicts, these clinicians must become aware of the abuse potential of the powerful narcotics they prescribe. Increased reference to state-maintained controlled medication databases can also reduce misprescribing.

Recent health care reform legislation has prompted greater efforts to divert substance abusers to addiction treatment facilities. A major component of reform has been the acknowledgement that mental health and addiction issues must be treated on a par with medical issues. The merger of the Haight Ashbury Free Clinics and Walden House offers a model for the medicalization of therapeutic communities to provide a medical home for previously underserved, marginalized populations.

Reviewing The Psychedelic Journey of Marlene Dobkin de Rios gave me many insights into this beautiful and brilliant woman, as well as answering questions I have had since we first met in the Haight...

Compelling clinical evidence establishes that buprenorphine is similar to methadone in efficacy for opiate detoxification and maintenance but safer than methadone in an overdose situation. The Drug Abuse Treatment Act of 2000 (DATA 2000) enabled US physicians with additional training to prescribe buprenorphine to a limited number of opiate-dependent patients. The sublingual tablets Subutex (R) (buprenorphine alone) and Suboxone (R) (a combination of buprenorphine and naloxone) meet the specifications of DATA 2000. Suboxone is intended to discourage intravenously administration and has less abuse potential than buprenorphine alone. Suboxone is generally recommended for maintenance treatment except for women who are pregnant. Subutex is recommended in treatment of pregnant women. A buprenorphine opiate withdrawal syndrome can occur in newborns. Although intravenous buprenorphine abuse is a significant public health problem in some countries, buprenorphine alone or in combination with naloxone has less potential for abuse than heroin and some prescription opiates, such as oxycodone. Pharmacotherapy from physicians' offices makes buprenorphine treatment acceptable to some opiate-dependent patients who would not accept treatment in traditional opiate-maintenance clinics. For reasons not adequately understood, some patients find discontinuation of buprenorphine following long-term use difficult. This article reviews the pharmacology of buprenorphine, summarizes evidence supporting the safety and efficacy of buprenorphine and provides clinical guidelines for treatment.

Substance abuse represents a significant underlying cause of the health issues faced in the United States, which severely impacts the nation's health care system and economy. Recently enacted parity legislation mandates that benefits for addiction and mental health treatment be provided on an equal footing with those for treatment for physical health. Diversion and abuse of prescription medications is growing in young people, with much of the diversion occurring between family and friends. Addiction has been accepted by mainstream medicine as a brain disease, and is associated with many other medical disorders. Early intervention and treatment for addiction provides extraordinary cost-benefit outcomes. Additional training for addiction professionals will be necessary. Stigmatization of substance abusers continues to exist at the state and federal levels, although research during the past 10 years indicates that patient compliance and relapse rates for substance abusers are not significantly different than those for individuals with other chronic diseases, e.g. diabetes, hypertension, and cardiac issues. While parity for addiction treatment has become policy at the federal level, great challenges lie ahead in funding access, facilities, and training, as well as redirecting societal perceptions and legislated penalties.