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.

Ketamine, originally synthesized in 1962, has gained increasing attention due to its rapid and sustained antidepressant effects in treatment-resistant depression (TRD). Unlike traditional antidepressants, ketamine acts on multiple neurotransmitter systems, including NMDA receptor antagonism and AMPA receptor potentiation, offering a novel mechanism for mood regulation. Beyond psychiatry, ketamine remains a valuable anesthetic and analgesic agent with applications in acute and chronic pain management. Its anti-inflammatory, neuroprotective, and potential antitumor properties further underscore its versatility in clinical medicine. Despite its therapeutic promise, ketamine poses challenges due to its dissociative and hallucinogenic effects, contributing to widespread recreational use. Chronic misuse is associated with adverse health outcomes, including bladder dysfunction and hepatobiliary complications. As a result, ketamine has been subject to increasing regulatory scrutiny, balancing its medical utility with concerns about abuse potential. The rediscovery of ketamine’s antidepressant effects in the early 2000s has revolutionized psychiatric treatment, particularly in TRD and suicidality. Recent studies have also explored its efficacy in bipolar depression, posttraumatic stress disorder, obsessive-compulsive disorder, and substance use disorders, expanding its therapeutic applications. Additionally, ongoing research aims to elucidate its long-term effects and optimize dosing regimens to maximize clinical benefits while minimizing risks. This review highlights ketamine’s multifaceted pharmacological properties, its evolution from an anesthetic to a novel psychiatric treatment, and its broader medical applications. As research advances, a comprehensive understanding of ketamine’s mechanisms and clinical implications will be crucial for optimizing its therapeutic potential while mitigating its risks.

Stimulants that act on the central nervous system have been used since antiquity for ritual and other uses. Organic chemistry techniques, especially those developed in Germany in the late 1800s, resulted in the isolation and structural determination of several important stimulants. Synthetic pathways for amphetamine and related stimulants were developed in the first half of the 19th century, and these new drugs were widely marketed. Awareness of abuse potential emerged soon after but was contested. Stimulants have been used to counteract fatigue and promote wakefulness during military operations, as well as to treat sleep disorders, since the 1930s. Methylphenidate was approved to treat children with behavioral problems in 1962, predating the recognition of attention deficit hyperactivity disorder (ADHD). Stimulant abuse became a political concern in the post-war period, initially with the use of “pep-pills” by long-haul truck drivers and later as drug dealing became common in night clubs, with new laws limiting availability passed in the early 1960s. They have also been used to increase athletic and cognitive performance. Stimulants are still first-line therapies for ADHD and some sleep disorders; however, newer-generation drugs have been developed with better safety profiles and lower abuse potential. Illicit stimulant use continues to be common in many countries.

Major depressive disorder (MDD) is a serious and often chronic illness that requires early and urgent treatment. Failing to provide effective treatment of MDD can worsen the illness trajectory, negatively impact physical health, and even alter brain structure. Early optimized treatment (EOT) of MDD, with a measurement-based approach to diagnosis, rapid treatment initiation with medication dosage optimization, frequent monitoring, and prompt adjustments in treatment planning when indicated, should proceed with a sense of urgency. In this article, we describe common barriers to providing an EOT approach to treating MDD at each phase of care, along with strategies for navigating these obstacles. Approaching the treatment of MDD with a greater sense of urgency increases the likelihood of symptom reduction in MDD, facilitating full functional recovery and a return to life engagement.

The term “betel” most accurately refers to the betel pepper (Piper betle). Confusingly, this term is also frequently used to refer to a street drug that often—but not always—includes the betel leaf as a constituent. This linguistic misdirection only intensifies with terms such as “betel nut,” which, in common usage, may refer to this same composite street drug or to a single isolated constituent of that street drug: the nut of the areca palm (Areca catechu), which is otherwise wholly unrelated to the betel pepper. This composite street drug, colloquially referred to as “betel” or “betel nut” or “betel quid,” is one of the most frequently used psychoactive substances in the world. It carries a cultural legacy spanning over 10,000 years and a current user base numbering in the hundreds of millions. Its primary psychoactive constituent is arecoline, a well-established parasympathomimetic agent. Early studies exploring arecoline’s ability to modulate cholinergic signaling pathways and exert therapeutic psychiatric effects on conditions such as Alzheimer’s disease were initially mired by intolerable parasympathetic side effects. Indeed, over the course of its long history, various hints regarding the therapeutic utility of arecoline have been obfuscated by a variety of challenges which have only recently been overcome. Now, developments in psychopharmacology and our growing understanding of neurochemical brain circuitry have unlocked a new mechanism of action by which arecoline-derived medications interact with dopaminergic processes to improve outcomes for schizophrenia patients. One such medication, xanomeline-trospium (Cobenfy), has emerged as the first such agent to receive U.S. Food and Drug Administration (FDA) approval for the treatment of schizophrenia and represents an entirely new class of pro-cholinergic medication within the field of psychiatry. Many in the field believe that this heralds the beginning of a new era of psychopharmacology: the era of muscarinic agonism. This article briefly described the fascinating journey from ancient betel nuts to modern muscarinic therapeutics.

This review article explores the legislative differences across Canadian jurisdictions with respect to involuntary admission and treatment pending appeal. Some jurisdictions restrict involuntary admission for mental illness to when there is a risk for serious bodily harm or physical impairment. However, the majority of jurisdictions recognize non-bodily harms or substantial mental or physical deterioration as grounds for involuntary admission when other criteria are met. Once a person is involuntarily admitted, jurisdictions differ on how treatment is authorized and whether treatment can commence while a person contests a finding of incapacity to treatment to the courts. Some jurisdictions permit treatment pending appeal while others do not. This article compares Canadian jurisdictions’ mental health legislation and addresses discrepancies through the lens of the Canadian Charter of Rights and Freedoms and the Canada Health Act.