Cannabis, cannabinoids and health: a review of evidence on risks and medical benefits.

The legalization of cannabis for medical and recreational purposes has progressed internationally. Cannabis and cannabinoids are advocated for a plethora of medical indications. An increasing number of medical and nonmedical users regularly consume large doses of delta-9-Tetrahydrocannabinol (THC), the main active component of cannabis. Aim: to summarize the evidence on (1) risks of recreational cannabis use and (2) effectiveness and safety of medicinal cannabis. Findings on recreational use: Cannabis is mostly used to experience its acute rewarding effects. Regular use of high THC products can produce addiction (cannabis use disorder or CUD). Acute consumption of high THC doses (including unintentionally) can cause time-limited mental, gastrointestinal, and cardiovascular problems and motor vehicle accidents. Chronic patterns of cannabis use have been associated with multiple adverse outcomes that are of particular concern among adolescents and young adults, such as, disrupted learning, impaired cognitive performance, reduced educational attainment and an increased risk of CUD, psychosis/schizophrenia, mood and anxiety disorders and suicidal behaviors. There is debate about the extent to which cannabis use is a cause of these adverse outcomes. Physical health risks (e.g., respiratory and cardiovascular, prematurity and restricted fetal growth, hyperemesis syndrome among others) have also been linked with repeated consumption of cannabis with a high THC content. Findings on medical cannabis use: Herbal cannabis, medicines from extracted or synthetized cannabinoids-often used as adjuvants to standard medicines-may produce small to modest benefits. This is primarily the case in treating chronic pain, muscle spasticity, chemotherapy-induced nausea and vomiting, and refractory epilepsy (in the case of cannabidiol, CBD). The evidence is inconclusive on their value in treating mental disorders and other medical conditions. Safety: Cannabis-based medicine is generally well tolerated. There is a risk of mild to moderate adverse effects and CUD.

Substance use, socio-demographic characteristics, and self-rated health of people seeking alcohol and other drug treatment in New South Wales: baseline findings from a cohort study.

OBJECTIVE: To investigate the demographic characteristics, substance use, and self-rated health of people entering treatment in New South Wales public health services for alcohol, amphetamine-type stimulants, cannabis, cocaine, or opioids use, by principal drug of concern. DESIGN: Baseline findings of a cohort study; analysis of data in patient electronic medical records and NSW minimum data set for drug and alcohol treatment services. SETTING, PARTICIPANTS: People completing initial Australian Treatment Outcomes Profile (ATOP) assessments on entry to publicly funded alcohol and other drug treatment services in six NSW local health districts/networks, 1 July 2016 - 30 June 2019. MAIN OUTCOME MEASURES: Socio-demographic characteristics, and substance use and self-rated health (psychological, physical, quality of life) during preceding 28 days, by principal drug of concern. RESULTS: Of 14 087 people included in our analysis, the principal drug of concern was alcohol for 6051 people (43%), opioids for 3158 (22%), amphetamine-type stimulants for 2534 (18%), cannabis for 2098 (15%), and cocaine for 246 (2%). Most people commencing treatment were male (9373, 66.5%), aged 20-39 years (7846, 50.4%), and were born in Australia (10 934, 86.7%). Polysubstance use was frequently reported, particularly by people for whom opioids or amphetamine-type stimulants were the principal drugs of concern. Large proportions used tobacco daily (53-82%, by principal drug of concern group) and reported poor psychological health (47-59%), poor physical health (32-44%), or poor quality of life (43-52%). CONCLUSIONS: The prevalence of social disadvantage and poor health is high among people seeking assistance with alcohol, amphetamine-type stimulants, cannabis, cocaine, or opioids use problems. Given the differences in these characteristics by principal drug of concern, health services should collect comprehensive patient information during assessment to facilitate more holistic, tailored, and person-centred care.

Guideline No. 425a: Cannabis Use Throughout Women's Lifespans - Part 1: Fertility, Contraception, Menopause, and Pelvic Pain.

OBJECTIVE: To provide health care providers with the best evidence on cannabis use with respect to women's health. Areas of focus include general patterns of cannabis use as well as safety of use; care for women who use cannabis; stigma; screening, brief intervention, and referral to treatment; impact on hormonal regulation; reproductive health, including contraception and fertility; sexual function; effects on perimenopausal and menopausal symptoms; and use in chronic pelvic pain syndromes. TARGET POPULATION: The target population includes all women currently using or contemplating using cannabis. OUTCOMES: Open, evidence-informed dialogue about cannabis use, which will lead to improvement in patient care. BENEFITS, HARMS, AND COSTS: Exploring cannabis use through a trauma-informed approach provides the health care provider and patient with an opportunity to build a strong, collaborative, therapeutic alliance. This alliance empowers women to make informed choices about their own care. It also allows for the diagnosis and possible treatment of cannabis use disorders. Use should not be stigmatized, as stigma leads to poor "partnered care" (i.e., the partnership between the patient and care provider). Multiple side effects of cannabis use may be mistaken for other disorders. Currently, use of cannabis to treat women's health issues is not covered by public funding; as a result, individual users must pay the direct cost. The indirect costs of cannabis use are unknown. Thus, health care providers and patients must understand the role of cannabis in women's health issues, so that women can make knowledgeable decisions. EVIDENCE: PubMed, EMBASE, and grey literature were searched to identify studies of "cannabis use and effect on infertility, contraception, perimenopause and menopausal symptoms, and pelvic pain" published between January 1, 2018 and February 18, 2021. All clinical trials, observational studies, reviews (including systematic reviews and meta-analyses), guidelines, and conference consensus statements were included. Publications were screened for relevance. The search terms were developed using the Medical Subject Headings (MeSH) terms and keywords (and variants), including cannabis, cannabinoids, marijuana, dexanabinol, dronabinol, tetrahydrocannabinol; the specific terms to capture women's health were estrogen, estradiol, medroxyprogesterone acetate, vaginal contraception, oral contraceptives, fertilization, amenorrhea, oligomenorrhea, pelvic pain, dysmenorrhea, endometriosis, interstitial cystitis, vulvodynia, and menopause. VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and weak recommendations). INTENDED AUDIENCE: All heath care providers who care for women. SUMMARY STATEMENTS: RECOMMENDATIONS.

Cannabis use disorder and the future risk of cardiovascular disease in parous women: a longitudinal cohort study.

BACKGROUND: Cannabis use is increasing in women of reproductive age, but whether cannabis use disorders increase the long-term risk of cardiovascular disease in this population is not known. Cannabis may cause tachycardia, hypertension, cerebral vasoconstriction, and other adverse cardiovascular effects and has been associated with acute myocardial infarction and stroke. Data on the long-term effects of cannabis on the cardiovascular system are more limited. We assessed the relationship between cannabis use disorders early in life and the future risk of cardiovascular disease in women. METHODS: We analyzed a longitudinal cohort of 1,247,035 pregnant women in Quebec, Canada, between 1989 and 2019. The main exposure was current or past history of cannabis use disorders at cohort entry. The main outcome measure included future hospital admission for any cardiovascular disorder during 18,998,986 person years of follow-up. We used Cox proportional hazards regression models adjusted for patient characteristics to compute hazard ratios (HR) and 95% confidence intervals (CI) for the association of cannabis use disorder with the later risk of cardiovascular hospitalization. RESULTS: Women with cannabis use disorders had a higher incidence of cardiovascular hospitalization than unexposed women (58.4 vs. 33.6 per 10,000 person years). Cannabis use disorder was associated with 1.48 times the risk of cardiovascular hospitalization (95% CI 1.27-1.72), compared with no cannabis use disorder. The association was greater for cannabis with concomitant use of other substances (HR 1.84, 95% CI 1.53-2.21) than for cannabis alone (HR 1.30, 95% CI 0.99-1.72). Cannabis use disorder was strongly associated with hemorrhagic stroke, even with adjustment for other substance use (HR 2.08, CI 1.07-4.05). CONCLUSIONS: Cannabis use disorders may increase the long-term risk of cardiovascular disease in women, particularly hemorrhagic stroke. However, some of the excess risk may be due to concomitant use of other substances.

The deleterious effects of cannabis during pregnancy on neonatal outcomes.

OBJECTIVES: To evaluate whether cannabis use during pregnancy is associated with adverse neonatal outcomes that are independent of cigarette smoking. DESIGN: Prospective cohort study. SETTING: Adelaide (Australia), Auckland (New Zealand), Cork (Ireland), and Leeds, London and Manchester (United Kingdom). PARTICIPANTS: 5610 pregnant nulliparous women with low risk pregnancies recruited for the Screening for Pregnancy Endpoints (SCOPE) study, November 2004 - February 2011. At 14-16 weeks of pregnancy, women were grouped by self-reported cannabis use. MAIN OUTCOME MEASURES: Infant birthweight, head circumference, birth length, gestational age, and severe neonatal morbidity or mortality. RESULTS: 314 women (5.6%) reported using cannabis in the 3 months before or during their pregnancy; 97 (31%) stopped using it before and 157 (50%) during the first 15 weeks of pregnancy, while 60 (19%) were still using cannabis at 15 weeks. Compared with babies of mother who had never used cannabis, infants of those who still used it at 15 weeks had lower mean values for birthweight (adjusted mean difference [aMD], -127 g; 95% CI, -238 to -17 g), head circumference (aMD, -0.5 cm; 95% CI, -0.8 to -0.1 cm), birth length (aMD, -0.8 cm; 95% CI, -1.4 to -0.2 cm), and gestational age at birth (aMD, -8.1 days; 95% CI, -12.1 to -4.0 days). The differences for all outcomes except gestational age were greater for women who used cannabis more than once a week than for those who used it less frequently. CONCLUSIONS: Continuing to use cannabis during pregnancy is an independent risk factor for poorer neonatal outcomes.

Candidiasis of the tongue in cannabis users: a report of 2 cases.

Cannabis, a psychoactive drug widely used for medicinal, recreational, and religious purposes, can have detrimental effects on several body systems, including the respiratory, cardiovascular, and central nervous systems. The use of cannabis in cigarette form can produce a series of oral alterations, including periodontitis, caries, xerostomia, a decreased salivary pH, and an increase in the density of Candida albicans. However, the occurrence of oral candidal lesions related to cannabis use is little reported in the literature. This article reports 2 cases of oral candidiasis associated with cannabis use. The adult male patients, both of whom were systemically healthy, had white and red spots consistent with oral candidiasis on the dorsal surface of the tongue. One of the patients also had a red lesion on an area of the hard palate that was in contact with the affected area of the tongue. Neither patient was currently undergoing antibiotic or corticosteroid treatment, and both reported frequent smoking of cannabis. One patient was initially treated with an oral suspension of nystatin without clinical improvement. Miconazole gel therapy was then prescribed, and clinical improvement was observed after 2 weeks. The patient did not stop smoking cannabis, and a recurrence of oral candidiasis was observed 6 months posttreatment. Treatment with miconazole gel was repeated, resulting in resolution of the infection. The second patient declined treatment. The reported cases demonstrate that, although it is infrequently reported, oral candidiasis may occur in cannabis smokers.

An epidemiological, developmental and clinical overview of cannabis use during pregnancy.

The objective of the current narrative literature review is to provide an epidemiological, developmental and clinical overview on cannabis use during pregnancy. Cannabis use in pregnancy poses major health concerns for pregnant mothers and their developing children. Although studies on the short- and long-term consequences of prenatal cannabis exposure are increasing, findings have been inconsistent or difficult to interpret due to methodological issues. Thus, consolidating these findings into clinical recommendations based on the mixed studies in the literature remains a challenge. Synthesizing the available observational studies is also difficult, because some of the published studies have substantial methodological weaknesses. Improving observational studies will be an important step toward understanding the extent to which prenatal exposure to cannabis influences neurodevelopment in the offspring. Therefore, further research on prenatal cannabis exposure and the long-term consequences to offspring health in representative samples are needed to guide and improve clinical care for pregnant women and their children. Future research should also investigate the role of policies on prenatal cannabis use.

Association Between Marijuana Use and Sexual Frequency in the United States: A Population-Based Study.

BACKGROUND: Marijuana use is increasingly prevalent in the United States. Effects of marijuana use on sexual function are unclear, with contradictory reports of enhancement and detriment existing. AIM: To elucidate whether a relation between marijuana use and sexual frequency exists using a nationally representative sample of reproductive-age men and women. METHODS: We analyzed data from cycle 6 (2002), cycle 7 (2006-2010), and continuous survey (2011-2015) administrations of the National Survey of Family Growth, a nationally representative cross-sectional survey. We used a multivariable model, controlling for demographic, socioeconomic, and anthropographic characteristics, to evaluate whether a relationship between marijuana use and sexual frequency exists. OUTCOMES: Sexual frequency within the 4 weeks preceding survey administration related to marijuana use and frequency in the year preceding survey administration. RESULTS: The results of 28,176 women (average age = 29.9 years) and 22,943 men (average age = 29.5) were analyzed. More than 60% of men and women were Caucasian, and 76.1% of men and 80.4% of women reported at least a high school education. After adjustment, female monthly (incidence rate ratio [IRR] = 1.34, 95% CI = 1.07-1.68, P = .012), weekly (IRR = 1.36, 95% CI = 1.15-1.60, P < .001), and daily (IRR = 1.16, 95% CI = 1.01-1.32, P = .035) marijuana users had significantly higher sexual frequency compared with never users. Male weekly (IRR = 1.22, 95% CI = 1.06-1.41, P = .006) and daily (IRR = 1.36, 95% CI = 1.21-1.53, P < .001) users had significantly higher sexual frequency compared with never users. An overall trend for men (IRR = 1.08, 95% CI = 1.05-1.11, P < .001) and women (IRR = 1.07, 95% CI = 1.04-1.10, P < .001) was identified showing that higher marijuana use was associated with increased coital frequency. CLINICAL IMPLICATIONS: Marijuana use is independently associated with increased sexual frequency and does not appear to impair sexual function. STRENGTHS AND LIMITATIONS: Our study used a large well-controlled cohort and clearly defined end points to describe a novel association between marijuana use and sexual frequency. However, survey responses were self-reported and represent participants only at a specific point in time. Participants who did not answer questions related to marijuana use and sexual frequency were excluded. CONCLUSION: A positive association between marijuana use and sexual frequency is seen in men and women across all demographic groups. Although reassuring, the effects of marijuana use on sexual function warrant further study. Sun AJ, Eisenberg ML. Association Between Marijuana Use and Sexual Frequency in the United States: A Population-Based Study. J Sex Med 2017;14:1342-1347.

The Formation of Marijuana Risk Perception in a Population of Substance Abusing Patients.

Risk perception has been shown to be protective with regard to marijuana use. Notably, the risk perception of marijuana in individuals with substance abuse problems varies significantly from that of the general public. Understanding how risk perception is formed in substance users could explain these differences and help predict the consequences of policy changes. Using this framework, we explored risk perception and its formation in a sample of substance abusing veterans. Semi-structured interviews were conducted with veterans who were receiving treatment for substance abuse. Interviews were recorded digitally, transcribed verbatim, and analyzed using inductive thematic analysis. A prominent perspective among the 31 participants was that marijuana is significantly different from other drugs because it is safe, not addictive, not associated with physical withdrawal, and has less overt behavioral effects than other substances. Many of these participants drew upon their own innocuous experiences with the drug in developing this perspective, more so than information from any other source. A contrasting narrative emphasized marijuana's capacity to cause negative social consequences, act as a gateway to the use of other, more harmful substances, and cause paranoia or worsen psychosis. In conclusion, individual experience with marijuana featured more prominently in informing risk perception than any other source of information. Our results and previous literature suggest that the significant disconnect between the individual experiences of substance users and the current clinical and legal policy towards marijuana may weaken the legitimacy of public policy or the authority of the medical community.

The effects of cannabis use on major adverse cardiovascular outcomes, mortality, cost of hospitalization, and cardiac arrhythmias: A Retrospective analysis using the national inpatient sample.

As cannabis use is rising and federal restrictions are easing, it is important to recognize its potential adverse cardiovascular effects for better risk stratification and informed guidance. We conducted a retrospective study using the National Inpatient Sample database from 2016 to 2019, where 39,992 subjects were enrolled. The extracted population was classified into two groups based on the presence of cannabis-related disorders. The primary outcomes of the study were cardiovascular-related adverse events, in-hospital mortality, total cost of hospitalization, and cardiac dysrhythmias. The study concluded that cannabis use disorder was not significantly associated with the likelihood of having a cardiovascular adverse event, cardiac dysrhythmias, or with the cost of hospitalization when controlling for other variables (p = 0.257, p=0.481 & p = 0.481, respectively). However, it was significantly associated with the likelihood of mortality (p < 0.0001). Further randomized trials are needed to confirm these findings and elaborate on identified associations.

Cannabis and anhedonia: A systematic review.

This paper employs a systematic review to examine the correlation between anhedonia and marijuana use, exploring whether individuals with anhedonia use marijuana as a coping mechanism or if marijuana use plays a role in the onset of anhedonia. The search utilised PubMed and Web of Science databases, following PRISMA guidelines for paper selection. A total of 21 papers were selected to address this inquiry, and assessments were carried out using the Risk of Bias in Non-randomized Studies of Exposures (ROBINS-E) tool. The results revealed that 17 studies exhibited moderate and low risk of bias. The evaluation encompassed a total of 12,427 participants, including both animals and humans. Experimental animal studies focused on exploring the association between cannabidiol (CBD) and anhedonia, while human studies primarily employed observational research, examining various forms of anhedonia in individuals with or without mental disorders such as depression or psychosis. These studies also delved into understanding the effects of anhedonia during adolescence and explored the causal relationship between these concepts. The findings indicate a reciprocal rather than unidirectional relationship, establishing that initial anhedonia predisposes individuals to cannabis use, and subsequent consumption significantly intensifies the anhedonia experienced. Particularly, the studies placed special emphasis on adolescents and individuals with mental disorders.

Pulmonary Embolism: A Complication of COVID-19 or Drug Abuse?

Our patient was a young male who had presented to the emergency room with complaints of shortness of breath for three days. His workup was suggestive of a pulmonary embolism. The patient had a history of COVID-19 pneumonia six months prior to this admission, from which he recovered completely. He denied use of recreational marijuana (smoking or edibles initially) but later accepted to smoking marijuana. In fact, he had increased the dose and frequency over the last six months. The COVID-19 infection had a strong impact on his mental health, which pushed him to increase marijuana use. Our case report highlights drug abuse as a risk factor for venous thromboembolism, confounded by the recent COVID-19 infection.

Recurrent Spontaneous Pneumothorax Secondary to Marijuana and Tobacco Abuse.

Primary spontaneous pneumothorax occurs in patients without apparent clinical lung disease, with a higher incidence in tall, thin males between the ages of 10 and 30. Tension pneumothorax is a life-threatening condition that can develop within minutes due to progressive air accumulation in the pleural space; mechanical pressure can lead to significant cardiorespiratory compromise. Tobacco association with a higher incidence of spontaneous pneumothorax has been well documented, but marijuana and spontaneous pneumothorax connection has not been well studied. However, it has been observed that patients who use marijuana and tobacco simultaneously have a higher incidence of spontaneous tension and larger pneumothoraces, as well as longer postoperative stay and higher recurrence than cigarette-only users. We present a case of a 26-year-old young male with a history only significant for excessive tobacco and marijuana smoking who developed multiple recurrent spontaneous pneumothorax and had to undergo right-sided video-assisted thoracoscopic surgery (VATS) with minimally invasive thoracotomy and had a prolonged hospital stay. With our case report, we hope to add to the evidence the effects of combined marijuana and tobacco smoking on bullous lung disease and pneumothorax while emphasizing the importance of conducting a detailed substance use history in patients with spontaneous pneumothorax.

Variant Angina and Cannabis-Induced Myocarditis: A Rare Presentation of Myocardial Inflammation.

Myocarditis is a rare but serious inflammatory disease of the myocardium, often caused by viral infections. We present a unique case of myocarditis in a previously healthy 29-year-old male who developed symptoms and electrocardiography changes of variant angina following cannabis use. This case report discusses the patient's atypical presentation, diagnostic evaluation, management, and outcome.

Risk factors for cannabis use disorders and cannabis psychosis in Japan: Second report of a survey on cannabis-related health problems among community cannabis users using social networking services.

AIM: To determine the risk factors for cannabis use disorders and cannabis psychosis in Japan based on a 2021 online survey among Japanese users of social network services. METHODS: The 3142 respondents who had used cannabis within the preceding year were categorized into two groups based on the development of cannabis use disorder and/or cannabis psychosis. Analyses were performed to determine these conditions' risk factors. RESULTS: Multivariate analysis revealed that factors significantly associated with cannabis use disorders were "cannabis-use initiation at a young age" (p = 0.004, OR: 0.951, 95% CI [0.920-0.984]), "family history of mental health problems" (p < 0.001, OR: 1.988, 95% CI [1.545-2.556]), "psychiatric disorders preceding cannabis use" (p = 0.039, OR: 1.672, 95% CI [1.026-2.722]), and "use of cannabis products other than dry flower" (p < 0.001, OR: 2.725, 95% CI [1.844-4.026]). Factors significantly associated with cannabis psychosis were "cannabis-use initiation at a young age" (p = 0.011, OR: 0.888, 95% CI [0.811-0.973]) and "family history of mental health problems" (p = 0.002, OR: 2.531, 95% CI [1.400-4. 576]). CONCLUSION: Risk factors for problematic cannabis use were cannabis initiation at a young age, pre-cannabis psychiatric disorders, family history of mental health problems, and the use of cannabis products other than dry flower. However, the causal relationship among these factors remains ambivalent.

Alcohol and cannabinoid binges and daily exposure to nicotine in adolescent/young adult rats induce sex-dependent long-term appetitive instrumental learning impairment.

Adolescence is a critical developmental period, concerning anatomical, neurochemical and behavioral changes. Moreover, adolescents are more sensitive to the long-term deleterious effects of drug abuse. Binge-like consumption of alcohol and marijuana, along with tobacco smoking, is a dangerous pattern often observed in adolescents during weekends. Nevertheless, the long-term effect of their adolescent co-exposure has not been yet experimentally investigated. Long-Evans adolescent male (n = 20) and female (n = 20) rats from postnatal day 30 (P30) until P60 were daily treated with nicotine (0.3 mg/kg, i.p.), and, on two consecutive 'binging days' per week (for a total of eight times), received an intragastric ethanol solution (3 g/kg) and an intraperitoneal (i.p.) dose of cannabinoid 1/2 receptor agonist WIN55,212-2 (1.2 mg/kg). These rats were tested after treatment discontinuation at > P90 for associative food-rewarded operant learning in the two-lever conditioning chambers for six consecutive days on a fixed ratio 1 (FR1) schedule followed by another six days of daily FR2 schedule testing, after 42 days rest. We found the main effects of sex x treatment interactions in FR1 but not in FR2 experiments. Treated females show attenuated operant responses for food pellets during all FR1 and the FR2 schedule, whilst the treated males show an impairment in FR2 but not in the FR1 schedule. Moreover, the treated females' percentage of learners was significantly lower than female controls in FR1 while treated males were lower than controls in FR2. Our findings suggest that intermittent adolescent abuse of common drugs, such as alcohol and marijuana, and chronic tobacco exposure can cause significant long-term effects on motivation for natural reinforcers later in adulthood in both sexes. Females appear to be sensitive earlier to the deleterious effects of adolescent polydrug abuse, with both sexes having an increased likelihood of developing lifelong brain alterations.

Myopericarditis Associated With Marijuana Intake: A Case Report and Literature Review.

A 26-year-old male who endorses daily cigarette smoking and marijuana vaping presented to the emergency department with acute onset of left-sided chest pain radiating to the left shoulder. Physical examination was unremarkable, but laboratory investigations showed elevated white blood cells, cardiac biomarkers including troponin and creatine kinase, and mildly elevated C-reactive protein levels and erythrocyte sedimentation rate. Electrocardiogram displayed subtle ST-segment elevation in a diffuse pattern, leading to a diagnosis of acute myopericarditis. The patient was treated with anti-inflammatory medication and supportive care and instructed to cease cannabis use.

Association between Substance Misuse and Outcomes in Critically III Patients with Pneumonia.

Rationale: In patients with pneumonia requiring intensive care unit (ICU) admission, alcohol misuse is associated with increased mortality, but the relationship between other commonly misused substances and mortality is unknown. Objectives: We sought to establish whether alcohol misuse, cannabis misuse, opioid misuse, stimulant misuse, or misuse of more than one of these substances was associated with differences in mortality among ICU patients with pneumonia. Methods: This was a retrospective cohort study of hospitals participating in the Premier Healthcare Database between 2010 and 2017. Patients were included if they had a primary or secondary diagnosis of pneumonia and received antibiotics or antivirals within 1 day of admission. Substance misuse related to alcohol, cannabis, stimulants, and opioids, or more than one substance, were identified from the International Classification of Diseases (Ninth and Tenth Editions). The associations between substance misuse and in-hospital mortality were the primary outcomes of interest. Secondary outcomes included the measured associations between substance misuse disorders and mechanical ventilation, as well as vasopressor and continuous paralytic administration. Analyses were conducted with multivariable mixed-effects logistic regression modeling adjusting for age, comorbidities, and hospital characteristics. Results: A total of 167,095 ICU patients met inclusion criteria for pneumonia. Misuse of alcohol was present in 5.0%, cannabis misuse in 0.6%, opioid misuse in 1.5%, stimulant misuse in 0.6%, and misuse of more than one substance in 1.2%. No evidence of substance misuse was found in 91.1% of patients. In unadjusted analyses, alcohol misuse was associated with increased in-hospital mortality (odds ratio [OR], 1.12; 95% confidence interval [CI], 1.06-1.19), whereas opioid misuse was associated with decreased in-hospital mortality (OR, 0.46; 95% CI, 0.39-0.53) compared with no substance misuse. These findings persisted in adjusted analyses. Although cannabis, stimulant, and more than one substance misuse (a majority of which were alcohol in combination with another substance) were associated with lower odds for in-hospital mortality in unadjusted analyses, these relationships were not consistently present after adjustment. Conclusions: In this study of ICU patients hospitalized with severe pneumonia, substance misuse subtypes were associated with different effects on mortality. Although administrative data can provide epidemiologic insight regarding substance misuse and pneumonia outcomes, biases inherent to these data should be considered when interpreting results.