Although Cannabidiol (CBD) has recently been approved for use in some neurological diseases, the pharmacology of CBD is not fully understood. Experimental reports suggest CBD inhibits a large number of enzymes, generating the possibility of multiple interactions. The aim is to describe the main known interactions, evidence, and actual risk in clinical practice. Existing indexed publications and product monographs were reviewed. The authors cataloged and classified the information based on the severity of the interaction, type (Pharmacokinetic vs. Pharmacodynamic), and level of evidence. 1,289 drug-drug interactions were identified (634 pharmacokinetic and 655 pharmacodynamic interactions). There were a total of 19 major interactions (colchicine, levomethadyl acetate, Mipomersen, propoxyphene, brexanolone, buprenorphine, esketamine, fezolinetant, ketamine, leflunomide, levoketoconazole, lomitapide, morphine, pexidartinib, pralsetinib, relugolix, sodium oxybate, teriflunomide, venetoclax), 393 moderate interactions, 49 minor interactions, and 828 of unknown significance. Drugs that should be avoided in the presence of cannabidiol, those that should be monitored, and those interactions that, while frequently mentioned, do not present sufficient evidence to recommend therapeutic changes are identified. The information highlights the need for caution. While many interactions have been postulated, only a small group warrants consideration in clinical practice. For the remaining drugs, special caution is needed. The long history of human use of the cannabis plant is often confused with the limited timeframe for scientific study of its isolated derivatives. The available information allows us to identify drugs with potential Drug-Drug Interactions of varying severity. This information can be used to improve treatment safety.

Idiopathic hypersomnia (IH) is a chronic central disorder of hypersomnolence characterized by excessive daytime sleepiness despite adequate or prolonged sleep, with potentially substantial effects on occupational functioning, cognition, and driving safety. Pharmacologic management may be challenging when treatment is limited by inadequate efficacy or adverse effects. We report a young woman with severe hypersomnolence and a diagnosis of IH supported by clinical history and objective sleep testing. Multiple sleep latency testing demonstrated a mean sleep latency of one minute and 22 seconds, with no sleep-onset rapid eye movement periods (SOREMPs). Her Epworth Sleepiness Scale (ESS) score was 18/24, and symptoms included prolonged sleep duration, extended daytime naps, occupational impairment, and drowsy driving. Modafinil initially produced substantial benefit but subsequently lost efficacy despite dose escalation. Sequential trials of armodafinil, solriamfetol, mixed amphetamine salts, and methylphenidate were limited by tachycardia, inadequate efficacy or poor tolerability, paranoia, and persistent late-day sleepiness, respectively. Lower-sodium oxybate was subsequently initiated at 3 g once nightly but was reduced to 2.25 g because of significant nausea. With slower, individualized titration to 5.5 g once nightly, the patient reported substantial improvement in daytime sleepiness and functioning. Her ESS score decreased from 18/24 to 4/24, scheduled methylphenidate and caffeine were no longer required, and daytime napping was markedly reduced. This case illustrates the challenges of longitudinal pharmacologic management of IH and highlights the importance of individualized treatment selection, tolerability-guided oxybate titration, and assessment of functional outcomes beyond standardized sleepiness scores.

The coexistence of multiple primary sleep disorders in a single patient is uncommon and poses significant diagnostic and therapeutic challenges. We report a 45-year-old woman with severe mixed sleep apnea (OSA/CSA), NREM parasomnia (night terrors), sleep-related eating disorder (SRED), nightmare disorder (with RBD like behavior but no REM atonia on PSG), and central hypersomnolence phenotype minimally affected with PAP optimization and delayed sleep-wake phase disorder. Symptoms began more than two decades earlier and included violent dream-enactment behaviors, hypnopompic hallucinations, sleep inertia, and chronic excessive daytime sleepiness (EDS). Treatment required multi-modal therapy. Positive airway pressure therapy successfully treated sleep disordered breathing while pitolisant and solriamfetol produced the most durable improvement in daytime sleepiness. Together melatonin plus clonazepam reduced parasomnia frequency and severity. Several other agents (including prazosin, sodium oxybate, paroxetine, and modafinil) were tried and discontinued for limited benefit or adverse effects. Notably, GLP-1 receptor agonist (GLP-1 RA) therapy for obesity was followed by a substantial weight loss and coincided with resolution of SRED. Because this occurred alongside improved sleep stability, PAP adherence, behavioral adaptation, and medication changes, causality cannot be inferred. The observation may justify further study of metabolic and incretin-related pathways in sleep-related eating behaviors. Overall, this case highlights the complexity of overlapping sleep-wake disorders, the need for individualized pharmacologic sequencing, and a potential emerging role for GLP-1 agonists in SRED.

Narcolepsy is a long-term brain disorder caused by disrupted orexin signaling. Orexin neurons sit in the hypothalamus and control the sleep-wake cycle; damage to these neurons leads to narcolepsy. Early evidence pointed to an autoimmune attack on orexin neurons as the main cause. Current treatments - stimulants, antidepressants, sodium oxybate, and scheduled naps - ease symptoms but do not stop the disease, and they often cause side effects such as anxiety, insomnia, and heart problems. Most of these drugs also cannot cross the blood-brain barrier (BBB) to act directly on the hypothalamus. This review examines the autoimmune basis of orexin neuron loss in narcolepsy and looks at how nanotechnology-based delivery systems could carry orexin peptides, genes, or antibodies across the BBB. We highlight priorities for future work: nano-enabled drug delivery, gene and peptide-based therapies, long-term safety data, and treatment approaches tailored to each patient. Progress in this area could shift narcolepsy care from symptom control toward real disease-modifying therapy.

Narcolepsy type 1 is a rare sleep disorder characterized by excessive daytime sleepiness (EDS) and cataplexy, thought to result from the immune-mediated destruction of hypocretin-producing neurons in genetically susceptible individuals. Viral infections have been implicated as potential environmental triggers. We present the case of a 17-year-old female National Collegiate Athletic Association (NCAA) Division I student-athlete with a prior diagnosis of idiopathic hypersomnia who developed new-onset cataplexy following COVID-19 infection. Initial polysomnography and multiple sleep latency testing demonstrated severe hypersomnolence without sleep-onset rapid eye movement periods. Several months later, she developed emotionally triggered episodes of muscle weakness consistent with cataplexy. Repeat multiple sleep latency testing demonstrated only one sleep-onset rapid eye movement period; however, given the development of typical cataplexy and the overall clinical presentation, a clinical diagnosis of narcolepsy type 1 was made. Cerebrospinal fluid hypocretin testing was not performed. Symptoms were refractory to multiple stimulant and antidepressant regimens but responded well to sodium oxybate in combination with solriamfetol, resulting in the resolution of EDS and cataplexy. This case highlights a possible temporal association between COVID-19 infection and the subsequent development of narcolepsy type 1 and underscores the importance of clinical judgment when objective diagnostic testing is inconclusive.

Sodium oxybate (SO) is an effective therapy for narcolepsy type 1 (NT1) but has been infrequently linked to complex sleep-related behaviors. We describe a case of NT1 who developed sleep-related eating disorder (SRED) after progressive gradual titration of SO. A 15-year-old female was diagnosed with NT1. Symptoms remained disabling despite high doses of modafinil and venlafaxine, and thus SO was initiated and titrated over months. After increasing to a dose of 4 g twice per night, the family reported episodes of partial arousal with altered consciousness beginning 1-2 h after the first dose, where the patient left the bed, ate large quantities of calorie-dense foods, and appeared unresponsive, before returning to bed again with complete amnesia. These episodes contributed to significant distress for the patient and her family, and notable weight gain. Gradual dose reduction to 7 g/night combined with structured behavioral interventions (dietary modification, bedside snacks, and environmental safety measures) successfully resolved SRED while maintaining excellent cataplexy control, demonstrating that combined management strategies can avoid medication discontinuation.

Sodium, calcium, magnesium and potassium oxybate are salts of gamma-hydroxybutyric acid (GHB). GHB is an endogenous substance and low amounts are normally found in breastmilk. Large doses of GHB have been used as a substance of abuse. Infants have been successfully breastfed by mothers taking sodium oxybate therapeutically for narcolepsy. With the typical 2 doses per night treatment regimen, nursing should usually be withheld from the time of the first dose to 4 to 6 hours after the second dose and breastfeeding can be continued during the day.[1] No information is available on the use or safety of GHB as a drug of abuse during breastfeeding.

BackgroundDrug-use in sexual settings among men who have sex with men (MSM) is increasing across Europe and is a key driver of sexually transmitted infections (STIs). Chemsex is evolving with increasing use of new psychoactive substances and diversification of context, shifting from private homes to diverse settings. Our aim was to assess changes in drug-use for sex among MSM who attended our STI/HIV reference center in two different periods over the last 8 years.MethodsWe compared two cross-sectional surveys conducted at the STI/HIV center of the San Gallicano Dermatological Institute (Rome, Italy) in 2018 (using paper-based, self-administered questionnaires) and 2024-2025 (using online self-administered questionnaires). The main outcome was the self-reported sexualized drug-use and chemsex (i.e., use of any of the three classic "chems": crystal methamphetamine, mephedrone, and GHB/GBL) in the previous year. Proportions were compared using Fisher's exact test or chi-square test, as appropriate.ResultsThe surveys included 354 MSM in 2018 and 331 MSM in 2024-2025. Overall, chemsex significantly increased from 5.1% in 2018 to 19.0% in 2024-2025 (p < 0.0001), both among MSM living with HIV (p < 0.0001) and MSM not living with HIV (p = 0.0005). A significant increase was observed in the use of crystal meth (2.3% vs 8.2%, p = 0.0005), mephedrone (4.0% vs 9.4%, p = 0.005), and GHB/GBL (3.4% vs 16.9%, p < 0.0001). Synthetic cathinones (from 0 to 2.7%, p = 0.001) and cannabinoids (from 0 to 0.9%, p = 0.112) emerged as new substances reported only in the most recent survey.ConclusionsIn our setting, drug-use for sex increased over time among MSM, with expansion of chemsex and diversification of substances. This behavioral change may increase STI/HIV transmission. Public health & STI/HIV services should update screening, counselling and harm reduction strategies to address these evolving patterns.

Pharmacological management has been the backbone of treatment for disorders of central hypersomnolence despite challenges in drug administration due to intolerable side effects, development of tolerance, and addiction potential. Recent advances in drug therapies for central hypersomnolence disorders, namely sodium oxybate and orexin agonists, have either changed or increased the potential to significantly improve the quality of life of individuals with narcolepsy and idiopathic hypersomnia. Mechanisms of action, pharmacodynamics and pharmacokinetics of previously and commonly used medications, along with the evidence behind their use, are discussed. In addition, oveporexton, an orexin receptor 2 agonist (OX2R) will be discussed as it marks an important first step in directly counteracting the pathology behind narcolepsy with cataplexy and has completed Phase 2 trials with Phase 3 underway. Early clinical data is promising; however, its long term efficacy and safety data is insufficient to garner US Food & Drug Administration approval, though additional trials are ongoing in narcolepsy with cataplexy, and non-orexin deficient central hypersomnolence disorders as well. Regardless, new drug developments may lead expanded treatment options and may have the potential to decrease or potentially eliminate the need for polypharmacy in the treatment algorithm for narcolepsy and idiopathic hypersomnia.