Cannabis has a long history as a medicine and was a part of medical practice until the late 19th century. The discovery of cannabidiol (CBD) and ∆9-tetrahydrocannabinol (THC) in the mid-20th century, and then the various components of the endocannabinoid system (ECS) over the following decades has again brought cannabis back into the public eye as a potential therapeutic agent. At present, cannabis is being used in the community across the world for both recreational and medical purposes. In the case of medical usage, it may be prescribed by a medical doctor or purchased either legally or illicitly for medical purposes such as symptom relief. Evidence for cannabis as a medicine is still an emerging field, and while potential mechanisms of action for a variety of conditions have been elucidated, including cancer, epilepsy, and chronic pain, high-quality randomized controlled trials in humans are still lacking. Despite popular beliefs, cannabis, like all other medicines, has potential benefits and harms, and long-term consumption of cannabis, even for medical reasons, may not be risk-free. In addition, consumption via modes of administration such as smoking or using a bong may increase the risk of negative health outcomes.

Anxiety disorders, characterized by excessive fear and behavioral disturbances, are among the most prevalent psychiatric conditions, yet treatment options remain suboptimal for many patients. Clonidine, an alpha-2 adrenergic receptor agonist, has shown potential anxiolytic effects and may address treatment-resistant cases. This review explores the efficacy, safety, and mechanism of clonidine as a pharmacological option for anxiety disorders, with emphasis on its role in modulating noradrenergic dysfunction and its potential synergistic effects with existing therapies. A literature review was conducted to evaluate clinical studies, case reports, and comparative trials on clonidine’s use in anxiety disorders, focusing on its pharmacological profile, efficacy, and tolerability. Evidence suggests clonidine may reduce anxiety symptoms, particularly in treatment-resistant cases and specific populations, such as pediatric patients and those with comorbid psychiatric disorders. Its mechanism involves modulating norepinephrine release and glutamatergic pathways. Case studies and small trials highlight its potential in reducing cognitive symptoms of anxiety, but inconsistencies in efficacy and side effects, including sedation and hypotension, were noted. Comparative studies suggest clonidine may have similar efficacy to SSRIs in some cases but lack large-scale validation. Clonidine presents as a promising pharmacotherapeutic option for anxiety disorders, particularly in cases resistant to conventional treatments or in patients with contraindications to other typical medications. Its mechanism of action, tolerability, and potential synergistic effects with existing therapies underscore the need for continued exploration and clinical trials to establish its optimal role in anxiety disorder management.

Parkinson’s disease (PD) is a severe neurodegenerative disorder characterized by prominent motor and non-motor (e.g., cognitive) abnormalities. Notwithstanding Food and Drug Administration (FDA)-approved treatments (e.g., L-dopa), most persons with PD do not adequately benefit from the FDA-approved treatments and treatment emergent adverse events are often reasons for discontinuation. To date, no current therapy for PD is disease modifying or curative. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are central nervous system (CNS) penetrant and have shown to be neuroprotective against oxidative stress, neuroinflammation, and insulin resistance, as well as promoting neuroplasticity. Preclinical evidence suggests that GLP-1RAs also attenuate the accumulation of α-synuclein. The cellular and molecular effects of GLP-1RAs provide a basis to hypothesize putative therapeutic benefit in individuals with PD. Extant preclinical and clinical trial evidence in PD provide preliminary evidence of clinically meaningful benefit in the cardinal features of PD. Herein, we synthesize extant preclinical and early-phase clinical evidence, suggesting that GLP-1RAs may be beneficial as a treatment and/or illness progression modification therapeutic in PD.

Suicide accounts for over 700,000 deaths per year globally and remains a public health priority. Evidence suggests that sleep-related interventions may be effective in reducing depressive symptom severity and suicidal thoughts in patients diagnosed with depression and comorbid insomnia. This study aims to systematically review the efficacy of sedative-hypnotics and/or cognitive behavioral therapy for insomnia (CBT-I) on measures of suicidality.

In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, PubMed, Medline, Cochrane Library, Embase, Scopus, and Web of Science were searched from inception to July 30, 2024. Studies were included if they (1) were randomized controlled trials (RCTs) and (2) reported on suicide-related measures associated with sleep interventions as a primary outcome, secondary outcome, or a safety measure. We endeavored to define and operationalize suicidality as suicidal ideation (SI), suicide attempts (SA), and suicide completion (SC). In cases where study authors failed to separate these three dimensions, the term “suicidality” was applied.

Eighteen studies were identified meeting inclusion criteria, comprised of studies investigating benzodiazepines (n = 2), Z-drugs (n=4), orexin receptor antagonists (ORAs) (n=8), and CBT-I (n=4). Zolpidem reduces SI as well as insomnia (linear association = 0.12, p<0.05) as evidenced by improvement on both the Columbia-Suicide Severity Rating Scale (C-SSRS) and the Scale for Suicide Ideation (SSI). ORAs were not associated with either an increase or decrease in suicidality. CBT-I alleviates SI in patients with insomnia (t = −3.35, p<0.05).

Effectively treating insomnia is associated with reduced SI. Available evidence suggests that Food and Drug Administration (FDA)-approved sedative-hypnotics do not increase the risk of suicidality.

In recent times, several longitudinal studies aimed at clarifying whether cannabis use during adolescence might play a causal role in the subsequent risk of developing bipolar disorder have been published. Although their methodological heterogeneity precludes any meta-analytic approaches, evidence from these studies can be systematically evaluated using the Bradford Hill criteria. A biological gradient is supported by evidence on the dose–response relationship between exposure severity and outcome. As such, the effect of cannabis use on bipolar disorder onset is likely to be strong, coherent, plausible, and based on a clear temporality. In addition, some analogies can be hypothesized between studies testing the possible causal role of cannabis in the development of bipolar disorder and those is schizophrenia. Cannabis may represent a precipitating agent inducing bipolar disorder in a multicausal model of individual vulnerability. However, this relationship seems to be only partially consistent and nonspecific, and the experimental evidence is strongly suggestive but, as yet, inconclusive. Nevertheless, in summary, it seems there is sufficient support for the hypothesis that cannabis use during adolescence may play a causal role in bipolar disorder, although further studies are needed to consolidate the evidence.