Medicinal marijuana is legally used in the USA in 33 states and the District of Columbia, while other 10 states allow consuming it for both recreational and medical proposes [1]. In 2018, marijuana legislation is being considered in extra 12 states. Other than the USA, Uruguay is the first country to fully legalize marijuana in 2013, followed by Canada in 2018. World Health Organization reported that about 2.5% of the world’s population—147 million people—are using marijuana, 10 times more than cocaine or opiates [2]. About 45–80% of patients have prescribed marijuana for managing their chronic pain conditions. It is even used in conjunction with a long-term opioid therapy in 39% patients [3].

Currently, Muslim majority countries enforce rigorous rules as marijuana has been a long debated issue, but there are countries such as the Islamic Republic of Iran where reformation is under consideration. Experience of medical marijuana with counterintuitive religious interpretations has led policymakers to review legal decisions in countries as Iran, yet to implement on national perspective [4]. Noteworthy, a pattern has been noted in the use of marijuana of its various forms (smoke, vapor, edible, concentrates, and topical) in different parts of the world where marijuana has been legalized either for medical or recreational purposes. A recently published national survey in the USA reported that 14.6% of the total population has used marijuana in the past years, while 8.7% of them used it in the past month. Moreover, states where recreational marijuana use has been legalized, have shown the highest incidence of marijuana smoke of 16%. On the other hand, only 11.4% has smoked marijuana in states where it was not legalized [5].

Medicinal marijuana has been approved for the treatment of diseases like HIV/AIDS, cancer, glaucoma, and posttraumatic stress disorder. In 2016, it was reported that the usage of medicinal marijuana helped head and neck cancer patients with long-term side effects of radiotherapy [6].

However, there is an alarming rise in cardiovascular and respiratory problems after its consumption. A CARDIA meta-analysis study reported that 38% of its 3500 participants used marijuana with a positive correlation between its usage, hypertension, and dyslipidemia, which may lead to coronary artery disease [7]. Impact of marijuana usage on the cardiovascular system (CVS) is still unclear, due to the small sample size of patients with acute myocardial infarction (AMI) used in those studies. However, Frost et al. in their study aimed to study long-term outcomes in marijuana users post-AMI and found no association between its consumption and long-term mortality in 2097 post-AMI patients with 109 marijuana users followed up to 18 years [8]. Recently in 2017, Desai et al. analyzed big data of patients (500,000), which reported 3 ± 8% increase in lifetime odds of AMI in marijuana users, but with no significant raise in-hospital mortality, compared to AMI in non-marijuana users [9]. A critical remark, that 1.2 million regular marijuana users for recreational in France reported approximately 2000 adverse events which considered a remarkably low complication rate, maybe due to under-reporting of marijuana use [10]. To further elucidate on this perspective, analyzed data from National Inpatient Sample (NIS) database showed males had a higher prevalence of arrhythmia compared to female counterpart due to usage of marijuana and all-cause inpatient mortality rate among hospitalized marijuana users with arrhythmia too had 15.9% of relative increased risk [11]. It has also been reported that such recreational use of marijuana has led to the increasing trend in the occurrence of major acute cerebrovascular and cardiovascular events especially stroke, epilepsy, acute myocardial infarction, congestive heart failure, and almost all subtypes of arrhythmia [12]. As most often illicit substance users are exposed to a variety of harmful agents like smoking, alcohol abuse, amphetamine or cocaine, consequently large Swedish cohort study did not find any significant association of incidence of early stroke among marijuana users when these potential confounders were adjusted [13]. This recent evidence conflicts with Westover et al. where researchers found ischemic stroke was associated with marijuana abuse and dependence [14]. These findings emphasize the necessity for further evaluation of the effect of marijuana usage on the CVS putting into consideration, its medical usage and doses, not a recreational point of view.

Contradictory findings are reported in literature regarding recommending or prohibiting the use of marijuana for various medical conditions.

In addition to Marijuana’s mentioned medical benefits, it is linked to various adverse effects regarding short-term use and long-term use. For short-term use, it may lead to disturbance in the short-term memory and cognitive functions; not only that but also psychosis in high doses [15]. Addiction to marijuana is connected to long-term use [16]. Furthermore; Marijuana’s heavy users showed slow brain development, lower IQ, symptoms of chronic bronchitis and chronic psychosis [17]. The association between cancer and marijuana use is under investigation; as studies on head and neck cancers reported contradicting results, another lung cancer studies supported no association, but some studies succeeded in linking between testicular cancer and marijuana usage [18].

Despite the lack of a thorough benefit-harm analysis, marijuana has proven effective for pain management, and as anti-emetic in the treatment of chemotherapy-induced vomiting and nausea. Synthetic marijuana analog such as nabilole, levonantradol, and tetrahydrocannabinol reported mildly effective in cancer chemotherapy emesis palliation [19]. Ironically, these agents were not compared to the newly available anti-emetic agents and also narrow therapeutic window demands careful titration of dosage which further limits its usage [20]. It also reduces patient-reported spasticity symptoms in patients with multiple sclerosis [21]. Surprisingly, a recent meta-analysis of 19 randomized clinical trials of moderate quality (11 trials of high risk of bias; 6 trials of unknown risk of bias; 2 trials of low risk of bias) concluded that cannabinoids are beneficial in the treatment of obstructive sleep apnea syndrome (two trials), fibromyalgia (two trials), chronic pain (eight trials), and multiple sclerosis (seven trials) [22]. On the other hand, there is insufficient evidence to be able to draw conclusions regarding therapeutic effects of marijuana use in various medical conditions, some of which are anxiety symptoms in individuals with social anxiety disorders, mortality, or disability in patients after traumatic brain injury or intracranial hemorrhage, glaucoma, cancers, motor symptoms associated with Parkinson’s disease, epilepsy, and mental health in patients with schizophrenia [21].

Sixteen states legalized posttraumatic stress disorder (PTSD) as an implication and primary reason for marijuana usage; therefore, marijuana is requested from more than one-third of PTSD patients [23–26]. A synthetic form of cannabis was explored and showed significant clinical improvement in nightmares and subsidence of PTSD symptoms in patients who were non-responsive to available traditional therapies. It is still tough to make clinical recommendations for the use of marijuana for PTSD, due to the contradictory data that exist and variety of included studies in systematic reviews including; experiences, case reports, and observational studies [27]. However, other observational studies showed that it is associated with increased severity of PTSD symptoms [24]. Unfortunately, it is unknown whether and to what degree these findings can be applied to general populations; thus, more research is required.