Hormonal and Metabolic Disorders of Human Immunodeficiency Virus Infection and Substance Abuse

There are an estimated 200 million users of an illicit drug in the world today. In addition, an estimated 40 million people are infected with the human immunodeficiency virus (HIV) and an estimated 180 million people are infected with the hepatitis C virus (HCV). Both the use of an illicit drug and the co-occurrence of infections are associated with a multitude of medical and health consequences including hormonal and metabolic disorders. Thus, the National Institute on Drug Abuse (NIDA), a part of the National Institutes of Health (NIH) hosted a workshop on hormonal and metabolic disorders of HIV among substance abusers. A number of clinicians and scientists participated and discussed a wide range of issues concerning hormones, nutrition and metabolic complications in HIV and substance abuse. Their observations and the recommendations they made for future research are presented in these proceedings. The readers are encouraged to contact the NIH staff (JK, FV) for technical guidance and programmatic priorities on the subject and directly contact the individual authors for collaborations.     

Integrin alpha2beta1 affects mechano-transduction in slowly and rapidly adapting cutaneous mechanoreceptors in rat hairy skin

The role of a transmembrane protein, integrin alpha2beta1, to modulate the neural responses of cutaneous mechanoreceptors to mechanical indentation was examined using an isolated skin-nerve preparation in a rat model. Skin and its intact innervation were harvested from the medial thigh of the hindlimb and placed in a dish containing synthetic interstitial fluid. Using a standard teased nerve preparation, the neural responses of single slowly or rapidly adapting mechanoreceptors (SA or RA, respectively) were identified and the afferents categorized according to standard protocols (i.e. response to constant stimuli). The most sensitive spot of a mechanoreceptor's receptive field was identified and then stimulated using controlled compressive stress (constant or dynamic loads between threshold and saturation load for SAs and RAs, respectively). Loads were applied before, during, and after passive diffusion into the skin of a function-blocking anti-integrin alpha2 monoclonal antibody (FBmAb) or one of two types of control antibodies (immunoglobulin G or a FBmAb conjugated with a secondary antibody). The sensitivities of both SA and RA mechanoreceptors were profoundly reduced in the presence of the FBmAb, while not changing the waveforms of their action potentials or their adaptation properties. Both control antibodies had no significant effect on mechanoreceptors' sensitivities. Following removal of the FBmAb, the effects in some neurons were partially reversible. Taken together, the data from this study support the hypothesis that integrin alpha2beta1 plays a significant role in modulating mechanoreceptive response to compressive indentation.     

Encoding of location and intensity of noxious indentation into rat skin by spatial populations of cutaneous mechano-nociceptors

The ability of a spatial population of cutaneous, Adelta, and C mechano-nociceptors to encode the location and intensity of a noxious, cutaneous indentation was examined using an isolated preparation in a rat model. Skin and its intact innervation were harvested from the medial thigh of the rat hindlimb and placed in a dish, with the corium side down, containing synthetic interstitial fluid. The margins of the skin were coupled to an apparatus that could stretch and apply compression to the skin. The skin was suspended on top of a deformable platform whose bulk, nonlinear, compressive compliance emulated that found in vivo. The isolated preparation facilitated examination of the spatial population response by eliminating the nonlinear geometry and inhomogeneous compressive compliance present in-vivo. Spatial population responses (SPR) were formed from recordings of single neurons that were stimulated by compressing the skin with an indenter (flat cylinder, 3-mm diam) at discrete intervals from the center of their receptive fields. SPR were composed of the neural responses (z axis) at each indentation location (x, y plane), and were analyzed quantitatively using nonlinear regression to fit an equation of a Gaussian surface. Both Adelta and C SPR accurately encoded the location and intensity of noxious indentation. The intensity of the stimulus was encoded in the peak neural response of the SPR, which had a nonlinear relationship to the compressive force. The location of the stimulus was encoded in the x, y position of the peak of the SPR. The position of the peak remained constant with increasing magnitudes of compressive force. The overall form of the SPR also remained constant with changes of compressive load, suggesting a possible role for encoding in the SPR some aspects of shape of a noxious stimulus.     

Cannabis/Cannabinoids for Treating COVID-19 Associated Neuropsychiatric Complications

COVID-19 epidemic has resulted in devastating mortality and morbidity consisting of socioeconomic and health effects that have included respiratory/pulmonary, cardiovascular, mental health and neurological consequences such as anxiety, depression, and substance use. Several effective vaccines have been developed and extensive efforts are underway to develop therapeutics to treat COVID-19. Cannabis and/or its product-cannabidiol (CBD) are being advertised for the treatment of COVID-19 associated mental/neurological complications and substance use disorders. However, research reviewed shows that there is insufficient data from clinical studies to support the use of cannabis or CBD for the treatment of COVID-19 associated mental health and neurological complications. Additional basic and clinical research is suggested to develop cannabis or cannabidiol for the treatment of mental health problems associated with coronavirus infection and or substance use disorders. In the meantime, it is important that the addiction physician/psychiatrist must caution while prescribing or recommending cannabis or CBD for treating such clinical indications.

Graphical abstract

Research shows that currently there is no clinical evidence to support the use of cannabis or any of its compounds including CBD for treating any of the neuropsychiatric complications of COVID-19. Thus, it is important that the addiction physicians/psychiatrists caution their patients from using cannabis or cannabis products for treating any such complications.

     

A Randomized Controlled Trial Comparing the Effects of Yoga With an Active Control on Ambulatory Blood Pressure in Individuals With Prehypertension and Stage 1 Hypertension

The purpose of this study was to compare the effects of yoga with an active control (nonaerobic exercise) in individuals with prehypertension and stage 1 hypertension. A randomized clinical trial was performed using two arms: (1) yoga and (2) active control. Primary outcomes were 24‐hour day and night ambulatory systolic and diastolic blood pressures. Within‐group and between‐group analyses were performed using paired t tests and repeated‐measures analysis of variance (time × group), respectively. Eighty‐four participants enrolled, with 68 participants completing the trial. Within‐group analyses found 24‐hour diastolic, night diastolic, and mean arterial pressure all significantly reduced in the yoga group (?3.93, ?4.7, ?4.23 mm Hg, respectively) but no significant within‐group changes in the active control group. Direct comparisons of the yoga intervention with the control group found a single blood pressure variable (diastolic night) to be significantly different (P=.038). This study has demonstrated that a yoga intervention can lower blood pressure in patients with mild hypertension. Although this study was not adequately powered to show between‐group differences, the size of the yoga‐induced blood pressure reduction appears to justify performing a definitive trial of this intervention to test whether it can provide meaningful therapeutic value for the management of hypertension.     

Pulmonary status of habitual cocaine smokers.

We determined the prevalence of respiratory symptoms and lung dysfunction in a large sample of habitual smokers of freebase cocaine ("crack") alone and in combination with tobacco and/or marijuana. In addition, we compared these findings with those in an age- and race-matched sample of nonusers of crack who did or did not smoke tobacco and/or marijuana. A detailed respiratory and drug use questionnaire and a battery of lung function tests were administered to (1) a convenience sample of 202 habitual smokers of cocaine (cases) who denied intravenous drug abuse and (2) a reference sample of 99 nonusers of cocaine (control subjects). The cocaine smokers (85% black) included the following: 68 never-smokers of marijuana, of whom 43 currently smoked tobacco and 25 did not, and 134 ever-smokers of marijuana (42 current and 92 former), of whom 92 currently smoked tobacco and 42 did not. The control subjects (96% black) included the following: 69 never-smokers of marijuana, of whom 26 currently smoked tobacco and 43 did not, and 30 ever-smokers of marijuana (18 current and 12 former), of whom 21 currently smoked tobacco and 9 did not. Cases smoked an average of 6.5 g cocaine per week for a mean of 53 months. The median time of the most recent use of crack prior to study was 19 days (range less than 1 to 180 days). After controlling for the use of other smoked substances, frequent crack use was associated with: (1) a high prevalence of at least occasional occurrences of acute cardiorespiratory symptoms within 1 to 12 h after smoking cocaine (cough productive of black sputum [43.7%], hemoptysis [5.7%], chest pain [38.5%], usually worse with deep breathing, and cardiac palpitations [52.6%]) and (2) a mild but significant impairment in the diffusing capacity of the lung.(ABSTRACT TRUNCATED AT 250 WORDS)