Daniel Gadsden Barrus

Bio: Daniel Gadsden Barrus is an academic researcher from Research Triangle Park. The author has contributed to research in topics: Cannabinoid & Cannabinoid receptor. The author has an hindex of 5, co-authored 7 publications receiving 160 citations. Previous affiliations of Daniel Gadsden Barrus include RTI International.

Tasty THC: Promises and Challenges of Cannabis Edibles.

Abstract: Food products containing cannabis extract (edibles) have emerged as a popular and lucrative facet of the legalized market for both recreational and medicinal cannabis. The many formulations of cannabis extracts used in edibles present a unique regulatory challenge for policy makers. Though edibles are often considered a safe, discreet, and effective means of attaining the therapeutic and/or intoxicating effects of cannabis without exposure to the potentially harmful risks of cannabis smoking, little research has evaluated how ingestion differs from other methods of cannabis administration in terms of therapeutic efficacy, subjective effects, and safety. The most prominent difference between ingestion and inhalation of cannabis extracts is the delayed onset of drug effect with ingestion. Consumers often do not understand this aspect of edible use and may consume a greater than intended amount of drug before the drug has taken effect, often resulting in profoundly adverse effects. Written for the educated layperson and for policy makers, this paper explores the current state of research regarding edibles, highlighting the promises and challenges that edibles present to both users and policy makers, and describes the approaches that four states in which recreational cannabis use is legal have taken regarding regulating edibles.

Vaping Synthetic Cannabinoids: A Novel Preclinical Model of E-Cigarette Use in Mice:

Abstract: Smoking is the most common route of administration for cannabis; however, vaping cannabis extracts and synthetic cannabinoids (“fake marijuana”) in electronic cigarette devices has become increasingly popular. Yet, most animal models used to investigate biological mechanisms underlying cannabis use employ injection as the route of administration. This study evaluated a novel e-cigarette device that delivers aerosolized cannabinoids to mice. The effects of aerosolized and injected synthetic cannabinoids (CP 55,940, AB-CHMINACA, XLR-11, and JWH-018) in mice were compared in a battery of bioassays in which psychoactive cannabinoids produce characteristic effects. The most potent cannabinoids (CP 55,940 and AB-CHMINACA) produced the full cannabinoid profile (ie, hypothermia, hypolocomotion, and analgesia), regardless of the route of administration. In contrast, aerosolized JWH-018 and XLR-11 did not produce the full profile of cannabimimetic effects. Results of time course analysis for hypothermia showed that aerosol exposure to CP 55,940 and AB-CHMINACA produced faster onset of effects and shorter duration of action than injection. The ability to administer cannabinoids to rodents using the most common route of administration among humans provides a method for collecting preclinical data with enhanced translational relevance.

Sex, species and age: Effects of rodent demographics on the pharmacology of ∆9-tetrahydrocanabinol.

Abstract: Cannabis edibles are becoming more common in an increasingly diverse population of users, and the impact of first pass metabolism on cannabis's pharmacological profile across age and sex is not well understood. The present study examined the impact of age, sex and rodent species on the effects of intraperitoneal (i.p.) delta-9-tetrahydrocannabinol (THC) and its primary psychoactive metabolite, 11-OH-THC, in rodent models of psychoactivity and molecular assays of cannabinoid receptor type-1 (CB1) pharmacology. Like oral THC, i.p. THC also undergoes first pass metabolism. In both species and sexes, 11-OH-THC exhibited marginally higher affinity (~1.5 fold) than THC and both served as partial agonists in [35S]GTPγS binding with equivalent potency; 11-OH-THC exhibited slightly greater efficacy in rat brain tissue. In ICR mice, 11-OH-THC exhibited greater potency than THC in assays of catalepsy (7- to 15-fold) and hypothermia (7- to 31-fold). Further, 11-OH-THC was more potent in THC drug discrimination (7- to 9-fold) in C57Bl/6 J mice, with THC-like discriminative stimulus effects being CB1-, but not CB2-, mediated. THC's discriminative stimulus also was stable across age in mice, as its potency did not change over the course of the experiment (~17 months). While sex differences in THC's effects were not revealed in mice, THC was significantly more potent in females Sprague-Dawley rats than in males trained to discriminate THC from vehicle. This study demonstrates a cross-species in the psychoactive effects of i.p. THC across sex that may be related to differential metabolism of THC into its psychoactive metabolite 11-OH-THC, suggesting that species is a crucial design consideration in the preclinical study of phytocannabinoids.

Synthesis and Pharmacological Evaluation of 1-Phenyl-3-Thiophenylurea Derivatives as Cannabinoid Type-1 Receptor Allosteric Modulators.

Abstract: We previously reported diarylurea derivatives as cannabinoid type-1 receptor (CB1) allosteric modulators, which were effective in attenuating cocaine-seeking behavior. Herein, we extended the structure-activity relationships of PSNCBAM-1 (2) at the central phenyl ring directly connected to the urea moiety. Replacement with a thiophene ring led to 11 with improved or comparable potencies in calcium mobilization, [35S]GTPγS binding, and cAMP assays, whereas substitution with nonaromatic rings led to significant attenuation of the modulatory activity. These compounds had no inverse agonism in [35S]GTPγS binding, a characteristic that is often thought to contribute to adverse psychiatric effects. While 11 had good metabolic stability in rat liver microsomes, it showed modest solubility and blood-brain barrier permeability. Compound 11 showed an insignificant attenuation of cocaine seeking behavior in rats, most likely due to its limited CNS penetration, suggesting that pharmacokinetics and distribution play a role in translating the in vitro efficacy to in vivo behavior.

Cannabis and mental illness: a review

Abstract: With the increasing push to legalize cannabis in Western nations, there is a need to gage the potential impact of this policy change on vulnerable populations, such as those with mental illness, including schizophrenia, mood, and anxiety disorders. This is particularly important as there are strong motives in these individuals to seek short-term reward (e.g., "getting high"). Nonetheless, data to support the beneficial effects of cannabis use in psychiatric populations are limited, and potential harms in patients with psychotic and mood disorders have been increasingly documented. This article reviews the effects of cannabis in people with mental illness. Then, we provide a reconciliation of the addiction vulnerability and allostatic hypotheses to explain co-morbidity addiction in mentally ill cannabis users, as well as to further aid in developing a rational framework for the assessment and treatment of problematic cannabis use in these patients.

Changing landscape of cannabis: novel products, formulations, and methods of administration

Abstract: Laws regulating cannabis have changed radically in the U.S. and abroad. Historically, users smoked dried cannabis flowers that contained Δ9-tetrahydrocannabinol (THC), the primary psychoactive component of cannabis, as the principal product constituent. Coincident with cannabis legalization and increased interest in medicinal use of the plant, there is now an expansive retail cannabis marketplace with novel cannabis products, formulations, and methods of administration. In this review, we describe emergent cannabis product chemotypes (e.g. THC-dominant, CBD-dominant, balanced or 'hybrid' with high concentrations of THC and CBD), product formulations (e.g. edibles, concentrates), and methods of administration (e.g. smoked, vaporized, orally ingested). Psychologists can play a pivotal role in studying the health impact of cannabis legalization and conducting research to inform product regulation.

New psychoactive substances: a review and updates:

Abstract: New psychoactive substances (NPS) are a heterogeneous group of substances. They are associated with a number of health and social harms on an individual and societal level. NPS toxicity and dependence syndromes are recognised in primary care, emergency departments, psychiatric inpatient and community care settings. One pragmatic classification system is to divide NPS into one of four groups: synthetic stimulants, synthetic cannabinoids, synthetic hallucinogens and synthetic depressants (which include synthetic opioids and benzodiazepines). We review these four classes of NPS, including their chemical structures, mechanism of action, modes of use, intended intoxicant effects, and their associated physical and mental health harms. The current challenges faced by laboratory testing for NPS are also explored, in the context of the diverse range of NPS currently available, rate of production and emergence of new substances, the different formulations, and methods of acquisition and distribution.