Endocannabinoid-Mediated Neuromodulation in the Olfactory Bulb: Functional and Therapeutic Significance

Societal issues and policy implications related to the use of cannabinoids, cannabis, and cannabis-based medicines for pain management.

The "transmitter-specific" retrograde axonal tracer 3H-D-aspartate has been used to demonstrate neurons in the olfactory bulb which putatively utilize aspartate and/or glutamate as their neurotransmitter and which send an axon either to the piriform cortex or within the bulb itself. Injections of 3H-D-aspartate into layer I of the anterior piriform cortex, in the zone of termination of axons from the olfactory bulb, labeled only a few cells in the main olfactory bulb, located in the mitral and external plexiform layers. Although these cells resembled mitral and tufted cells, they tended to have smaller somata than other mitral or tufted cells and apparently form a distinct subpopulation of relay cells. In contrast, many of the mitral cells of the accessory olfactory bulb were labeled by the same injections of 3H-D-aspartate, probably as a result of involvement of the accessory olfactory tract or its bed nucleus in the injection site. Similar injections of the "nonspecific" tracer HRP into the anterior piriform cortex labeled most of the cells in the mitral cell layer of both the main and accessory olfactory bulbs, and some tufted cells in the external plexiform layer. It is concluded that only a small, distinct subpopulation of the mitral or tufted cells of the main olfactory bulb are aspartatergic and/or glutamatergic, while many (at least) of the mitral cells of the accessory olfactory bulb use the excitatory amino acids as transmitters. Injections of 3H-D-aspartate directly into the main olfactory bulb also failed to label the mitral and deeply situated tufted cells. However, a few cells were labeled in the periglomerular region, the superficial external plexiform layer, and the granule cell layer near the injection site. These labeled cells were smaller than mitral and tufted cells but generally larger than periglomerular or granule cells. They may represent a population of glutamatergic or aspartatergic short axon cells. In addition, small cells of an unknown type were labeled in the olfactory nerve layer following injections in the deepest part of the bulb. These cells do not correspond to any of the well characterized cell types of the olfactory bulb.

BackgroundMost U.S. states have legalized cannabis for medical and/or recreational use. In a 6-month prospective observational study, we examined changes in adult cannabis use patterns and health perceptions following broadened legalization of cannabis use from medical to recreational purposes in California.MethodsRespondents were part of Stanford University’s WELL for Life registry, an online adult cohort concentrated in Northern California. Surveys were administered online in the 10 days prior to state legalization of recreational use (1/1/18) and 1-month (2/1/18–2/15/18) and 6-months (7/1/2018–7/15/18) following the change in state policy. Online surveys assessed self-reported past 30-day cannabis use, exposure to others’ cannabis use, and health perceptions of cannabis use. Logistic regression models and generalized estimating equations (GEE) examined associations between participant characteristics and cannabis use pre- to 1-month and 6-months post-legalization.ResultsThe sample (N = 429, 51% female, 55% non-Hispanic White, age mean = 56 ± 14.6) voted 58% in favor of state legalization of recreational cannabis use, with 26% opposed, and 16% abstained. Cannabis use in the past 30-days significantly increased from pre-legalization (17%) to 1-month post-legalization (21%; odds ratio (OR) = 1.28, p-value (p) = .01) and stayed elevated over pre-legalization levels at 6-months post-legalization (20%; OR = 1.28, p = .01). Exposure to others’ cannabis use in the past 30 days did not change significantly over time: 41% pre-legalization, 44% 1-month post-legalization (OR = 1.18, p = .11), and 42% 6-months post-legalization (OR = 1.08, p = .61). Perceptions of health benefits of cannabis use increased from pre-legalization to 6-months post-legalization (OR = 1.19, p = .02). Younger adults, those with fewer years of education, and those reporting histories of depression were more likely to report recent cannabis use pre- and post-legalization. Other mental illness was associated with cannabis use at post-legalization only. In a multivariate GEE adjusted for sociodemographic characteristics and diagnoses, favoring legalization and the interaction of time and positive health perceptions were associated with a greater likelihood of using cannabis.ConclusionsLegalized recreational cannabis use was associated with greater self-reported past 30-day use post-legalization, and with more-positive health perceptions of cannabis use. Future research is needed to examine longer-term perceptions and behavioral patterns following legalization of recreational cannabis use, especially among those with mental illness.

The use of cannabis among college students is increasing. Cannabis abuse has been proposed to be associated with personality dimensions. However, there are currently no known studies on the relationship of temperament traits and recreational cannabis use among college students. This is a cross-sectional study that investigated 328 students at a Podiatric Medical College. We evaluated the association between temperament and recreational cannabis use by the students. Temperament was investigated using the Memphis, Pisa, Paris and San Diego Auto- Questionnaire (TEMPS-A (short version)). Additionally, we assessed demographics variables and perceived stress in the context of cannabis use, and analyzed the findings using logistic regression. The prevalence of recreational cannabis use was 8.45%. Recreational cannabis use among these students was highly associated with irritable and cyclothymic temperament traits. There was no association between recreational cannabis use and perceived stress, and demographic variables or other substance use. Furthermore, logistic regression analysis indicated that higher scores in cyclothymic or irritable temperament traits are significant predictors for recreational cannabis use. Our study has identified key temperament traits, with a strong association with recreational use of cannabis of the studied student population. Our findings are useful in designing screening and educational strategies directed towards increasing the wellbeing of medical students.

There has been considerable debate around the liberalization of cannabis laws in many countries. Given recent changes in cannabis policy, and the current discussion regarding cannabis legalization in Ireland, the aim of this study was to examine changes in attitudes over time towards permitting recreational cannabis use. We analyzed data from Ireland's 2002/03 (n = 4918); 2006/07 (n = 4967); 2010/11 (n = 5119); 2014/15 (n = 5937); 2019/20 (n = 3982) National Drug Prevalence Surveys. Multivariable logistic regression analyses were used to examine factors associated with being in favour of the use of cannabis for recreational purposes. The results indicate that there is minority support for permitting recreational cannabis use, which ranged from 19.1% in 2006/07 to 29.9% in 2019/20. In multivariable analysis being male and living in Dublin were significant predictors of agreeing with recreational cannabis use, as were being either a recent or past cannabis user, knowing cannabis users, perceiving cannabis use as not being a great risk, and not disapproving of cannabis use. Subjects aged less than 35 years and those who had completed primary education only were significantly less likely to agree with permitting recreational cannabis use. The results from this study indicate that there is minority support for allowing recreational cannabis use. Support was highest among recent cannabis users, consistent with previous studies. The relative lack of support for recreational cannabis use among younger respondents was surprising and warrants further research.

The sale of cannabis for adult recreational use has been made legal in nine US states since 2012, and nationally in Uruguay in 2013 and Canada in 2018. We review US research on the effects of legalization on cannabis use among adults and adolescents and on cannabis-related harms; the impact of legalizing adult recreational use on cannabis price, availability, potency and use; and regulatory policies that may increase or limit adverse effects of legalization. The legalization of recreational cannabis use in the US has substantially reduced the price of cannabis, increased its potency, and made cannabis more available to adult users. It appears to have increased the frequency of cannabis use among adults, but not so far among youth. It has also increased emergency department attendances and hospitalizations for some cannabis-related harms. The relatively modest effects on cannabis use to date probably reflect restrictions on the number and locations of retail cannabis outlets and the constraints on commercialization under a continued federal prohibition of cannabis. Future evaluations of legalization should monitor: cannabis sales volumes, prices and content of tetrahydrocannabinol; prevalence and frequency of cannabis use among adolescents and adults in household and high school surveys; car crash fatalities and injuries involving drivers who are cannabis-impaired; emergency department presentations related to cannabis; the demand for treatment of cannabis use disorders; and the prevalence of regular cannabis use among vulnerable young people in mental health services, schools and the criminal justice system. Governments that propose to legalize and regulate cannabis use need to fund research to monitor the impacts of these policy changes on public health, and take advantage of this research to develop ways of regulating can-nabis use that minimize adverse effects on public health.

Background: Adolescents and young adults have high rates of cannabis use. Although a sizeable portion of youth report that they use cannabis for medicinal reasons (Wardell et al., 2020; Wardell, in press), most research on youth cannabis use tends to focus on recreational use. It is important to understand how youth who use cannabis for medicinal reasons differ from those who use for recreational reasons. We aimed to review the limited research comparing youth engaging in medicinal cannabis use to those engaging in recreational cannabis use. Methods: A systematic literature search of three databases (PsychInfo, PubMed, MEDLINE) was conducted to identify studies that compared adolescents and/or young adults who engage in medicinal cannabis to those who engage in recreational cannabis use. Studies that defined medicinal cannabis use either as self-reported use of cannabis for therapeutic reasons or as obtaining authorization/prescription for medical cannabis from a healthcare provider were included. Only quantitative research studies published in a peer-reviewed journal were included. After conducting the initial search and removing duplicates, 748 abstracts were reviewed independently by two researchers. Any discrepancies were resolved by consensus in consultation with a third researcher. Results: A total of 13 articles met inclusion criteria. Outcome variables reported in the literature included cannabis use (frequency and amount), cannabis-related problems, use of other substances including illicit drug use or prescription medication misuse, and health-related variables such as mental health symptoms or physical pain. Overall, the literature suggests that youth who use cannabis medicinally are more likely to use greater amounts of cannabis, to use more frequently, and to use a variety of different forms of cannabis, relative to youth who use cannabis recreationally. Further, several studies reported that medicinal cannabis use among youth was associated with problems related to cannabis use, such as the risk for cannabis use disorder and problematic behaviour (e.g., driving under the influence). Several studies also found that medicinal (vs. recreational) cannabis use was related to poorer mental or physical health, although a couple of studies did not support this finding. However, the results were mixed regarding the associations between medicinal cannabis use and the likelihood of using other drugs. Conclusion: There is evidence that using cannabis for medicinal reasons is associated with greater cannabis consumption, cannabis-related problems, and negative health-related correlates among youth. Although there was some consistency in findings across studies, the limited number of studies make it difficult to draw firm conclusions. Causal inferences are difficult to make owing to the frequent reliance on cross-sectional designs. The findings are further complicated by the heterogeneous definition of medicinal cannabis use (i.e., self-report vs. medically authorized). Given that many young people engage in both medicinal and recreational cannabis use, it is difficult to fully disentangle the differences. Additional research is needed for a complete understanding of the unique outcomes associated with medical cannabis use among youth.

Theoretical reconstruction of field potentials and dendrodendritic synaptic interactions in olfactory bulb.

Cannabis is one of the oldest psychoactive substances in India and worldwide. Many developed countries like Canada, Netherlands and few states of the USA have legalized the use of recreational cannabis. However, In India, the recreational use of cannabis and its various forms such as ganja, charas, hashish, and its combination is legally prohibited. There have been several discussions and public interest litigations in India regarding the legalization of recreational cannabis use and its benefits. With this background, this article addresses the various implications of legalizing recreational use of cannabis, a multibillion dollar market and its impact on mental health, physical health, social, cultural, economic, and legal aspects with the lessons learnt from other countries that have already legalized recreational cannabis use. It also discusses whether India is prepared for the legalization of recreational cannabis, given the current criminal justice and healthcare systems. The authors conclude that, India is perhaps not enough prepared to legalize cannabis for recreational use. India's existing criminal justice and healthcare systems are overburdened, finding it challenging to control medicinal use, which is often the first contact point for cannabis-related concerns.

Prolactin promotes the recruitment of main olfactory bulb cells and enhances the behavioral exploration toward a socio-sexual stimulus in female mice

Municipal socioeconomic environment and recreational cannabis use in Mexico: Analysis of two nationally representative surveys.

Since California legalised medical use of cannabis in 1996, 29 other US states have done so. Eight US states have legalised the retail sale of cannabis to adults over the age of 21 years since 2012. Critics of these policy changes have suggested that they will increase the prevalence of cannabis use and cannabis use disorders. This paper (1) briefly describes the types of regulatory regimes for medical and recreational cannabis use in the USA, (2) describes possible effects of these policies on cannabis use and (3) assesses the impacts to date of the legalisation of medical and recreational cannabis use on the prevalence of cannabis use and cannabis use disorders in the US population. We (1) describe the regulatory regimes for medical and recreational cannabis use in the USA, (2) make predictions about their possible effects on the price and availability of cannabis, (3) conduct a review to summarise studies of the effects of legalising medical cannabis use in the USA on rates of cannabis use and cannabis use disorders and (4) assess early indications of the effects of legalising recreational cannabis use on cannabis use and cannabis use disorders. Liberal forms of medical cannabis regulation have probably reduced prices and increased the availability of cannabis. Analyses of survey data suggest that these changes have increased the prevalence and frequency of cannabis use among adults over the age of 21 years, but they have not to date increased rates of cannabis use among adolescents. Two series of epidemiological studies over a decade following the introduction of medical cannabis laws have produced inconsistent results on the effects of policy changes on the prevalence of cannabis use disorders in adults. One study found that the prevalence had increased; the other did not find an increase. An analysis of data on treatment seeking for cannabis use disorders showed an increase in states with medical cannabis laws in the number of adults seeking treatment who were not under legal coercion. There are major limitations with these studies, many of which have mistakenly assumed that all states with medical cannabis laws have similarly liberal policies. It may be a decade or more before we can fully assess the effects of liberalisation of cannabis policies on cannabis use and cannabis use disorders in the USA. It is critical that the effects of these policy changes are evaluated to ensure that cannabis is regulated in ways that minimise the harmful effects of its regular use, especially among young people.

The legality, recreational and medical use of cannabis varies widely by country and region but remains largely prohibited internationally. In October 2018, Canada legalized the recreational use of cannabis—a move many viewed as controversial. Proponents of legalization have emphasized the potential to eradicate the marijuana black market, improve quality and safety control, increase tax revenues, improve the availability of medical cannabis, and lower gang-related drug violence. Conversely, opponents of legalization have stressed concerns about cannabis’ addictive potential, second-hand cannabis exposure, potential exacerbation of underlying and established mental illnesses, as well as alterations in perception that affect safety, particularly driving. This systematic review synthesizes recent international literature on the clinical and public health implications of cannabis legalization.

Short term treatment with estradiol decreases the rate of newly generated cells in the subventricular zone and main olfactory bulb of adult female mice

Distinct distribution of four Ca 2+-dependent subtypes of protein kinase C in rat olfactory bulb; definite expression of βII-subtype in the accessory olfactory bulb