There is substantially less scientific research that has explored the chemical characterization of marijuana cigarette smoke and most studies have focused on determining cannabinoids in marijuana smoke and reported it to contain most of the same toxins, irritants and carcinogens commonly present in tobacco smoke.²⁹ For instance, when smoked, marijuana produces more tar with more concentrations of carcinogens such as benzo[a]pyrene as compared to tobacco smoke, and consequently it has been classified as a secondary carcinogen possessing 50% to 70% more carcinogenic polycyclic aromatic hydrocarbons such as benzo[a]anthracene, benzene and phenols in greater amounts alongside toxic gases and reactive oxygen species 20 times higher than in tobacco.³⁰ Notably, these variations in carcinogenic compound concentration in marijuana increase its probability of causing lung cancer in the same way tobacco does, and which has been credited as the leading cause of lung cancer.²⁹ Nevertheless, it can be presumed that smoking of marijuana is a precursor for respiratory disease and cancer similar to those caused by tobacco smoking, but on the other hand, there is minimal literature reporting or demonstrating that marijuana smoking causes cancer.³¹ Furthermore, it has been suggested that marijuana smoke comprises of particulate matter that is harmful and carcinogenic when inhaled because it contains potent compounds such as volatile organics and aromatic amines.²⁹

Smokers are driven to smoke marijuana due to its induced psychotropic effects characterized by pleasurable feeling, euphoria and relaxation with psychotic symptoms, cognitive changes, panic reactions and anxiety having been reported as the severe side effects.³²Epidemiological evidence has linked lung disease, increased respiratory and cardiovascular symptoms, chronic bronchitis and chronic obstructive disease and emphysema to marijuana smoking.³³ In some instances, marijuana use causes alterations and sometimes loss in memory characterized by slowed reaction time, hampered information processing, un-coordinated motor perceptions and performance, and attention deficiency that result in mood syndrome, psychosis and schizophrenia.³⁴ Accordingly, a review on the effects of marijuana smoking on the lungs found out that prolonged cannabis smoking leads to lung cancer and cancers of the upper aero digestive tract³⁵. Moreover, a brief exposure to second hand marijuana smoke leads to acute vascular endothelial dysfunction³⁶. Nonetheless, luck of sane mental control due to the detrimental effects of cannabis in intoxicated drivers has been reported to increase the risks of road accidents.³⁷The occurrence of these events is hypothesized by the fact that when one smokes marijuana joint he/she is four times exposed to carbon monoxide and five times more tar deposition than a single tobacco cigarette, due to more deep inhalation and longer holding breath times and luck of cannabis cigarette filters.³³ Consequently, psychiatric disorders in marijuana smokers have been associated with acute and chronic smoking.³⁸ As a result, young cannabis users are likely to experience a deficiency in mental performance by displaying slowness in information processing, amnesia and deprived attention which adversely affects their learning faculties.³⁴ In addition, pregnant women who get exposed to cannabis are more likely to experience weakened visualization and dexterity and give birth to children that are prone to abnormal behaviour in their late developmental stages.¹

Once the presence of cannabis is detected in the human central nervous system (CNS), it excites the production of dopamine and endogenous opioids with inhibition of the secretions of acetylcholine that result to pharmacological changes in the brain and a consequential decrease of glutamatergic synaptic transmission which causes brain functioning abnormalities among cannabis smoking community.³⁹ The endocannabinoid system receptors, CB1 and CB2 offer inhibitory function, where CB1 receptor act on the production of cyclic adenosine monophosphate pathway once they receive a signal by adenyl cyclase inhibitor activation while CB2 receptor plays a role in blocking inflammatory activity and tissue damage.¹ Therefore, brain structural abnormality has been observed in chronic cannabis smokers with more effects imposed on the grey and white matter density.³⁴ Further, variable brain activity in cannabis consumers has been reported compared to non-smokers in which greater brain activation is observed in the prefrontal region of smokers while hypo-activation is noted along the left superior parietal cortex due to high concentrations of the two cannabinoids THC and CBD, THC alters the hippocampal capacity and neurochemistry while on the other hand, CBD defends against toxic variations.⁴⁰

Nonetheless, cerebral stroke, one of the leading causes of death has been associated with cannabis intake according to a number of preclinical studies and scientific case reports.⁴¹Scientifically, neurological stroke and Alzheimer’s disease solely result from exposure to reactive oxygen species such as peroxynitrite, hydrogen peroxide, epoxides etc. and oxidative stress pathways that cause tissue and cellular damage which is largely promoted by cannabis smoking.¹ Accordingly, THC is a potential agent of oxidative stress and a threat factor in the initiation of ischemic stroke.⁴² Reactive oxidative stress compounds can be generated by combustion reactions that occur during marijuana smoking.

Pharmacological and toxicological properties of cannabis are contributed by eighteen classes of chemicals which include hydrocarbons, sugars, simple fatty acids, terpenes, amino acids, and nitrogenous compounds.⁴³ Accordingly, cannabis has been reported to find its application in medicine in treating oncology patients⁴⁴, epileptic patients⁴⁵, management of inflammatory bowel disease⁴⁶, neurological and psychiatric disorders³⁴ and sometimes in children to treat autism spectrum disorder, fetal alcohol spectrum disorder and in pregnant mothers in the management of hyperemis gravidarum.⁷ This has been attributed to the non-psychoactive cannabinoid CBD which interacts with the CB2 receptor that gets activated to reduce pain, seizures and inflammations in patients and sometimes in the management of epilepsy, schizophrenia and post-traumatic stress disorders.¹ Evidently, therapeutic capacity of THC against chronic pain and sclerosis neurological ailments has also been reported.³⁴ Some studies have reported the application of marijuana in in the treatment of HIV patients to improve their food intake by helping in their appetite and increasing ghrelin and leptin hormones, and decreasing peptide tyrosine hormone responsible for appetite regulation.⁴⁷

In addition, the application of medicinal marijuana in management of corona virus disease 2019 (Covid-19) has been explored by a couple of scientific studies. Covid-19 is and infectious disease that occurs as a result of the SARS-CoV-2 in humans⁴⁸, which has not found any medical cure by the time this review, was done. Therefore in the search for a vaccination or cure, the application of Marijuana has been explored by scientists who have given preliminary findings showing that the plant may offer resistance to SARS-CoV-2.⁸The principle behind this is based on the fact that medicinal cannabis has been used to treat nausea and dementia, therefore offering hopes that the angiotensin converting enzyme II (ACE-2) receptor needed by the corona virus found in the lung tissues, oral and nasal mucus, and gastrointestinal tracts can be modulated using cannabis extracts and removed from these parts in order to inhibit vulnerability to the virus and thereof reduce infection risk.⁴⁹ Furthermore, terpenes from cannabis have exhibited potent characteristics as antiviral agents with the ability to minimize severity and impact of SARS virus by suppressing the protein responsible for RNA replication and thereby blocking the virus from penetrating the cells.⁸ For instance, it has been emphasized that marijuana extracts can reduce or regulate serine protease TMPRSS2 mainly required by the SARS-Cov-2 in order for the virus to gain entry into the human host cells.^{8, 9} Consequently, cannabis has been reported to be effective in preventing and treating Covid-19 even though there is limited scientific studies that have been performed to support or refute these assertions especially the role played by cannabinoids towards viral therapy.⁵⁰

Cannabis just like any other drug substance once taken into the body system describes a systematic pathway from the time it gains entry into the body system up to the time it is excreted after series of biological activities that involve absorption, distribution, metabolism and excretion, all which are dependent on the drug bioavailability that determines the onset, duration and the intensity of effects manifested by the drug.⁵¹ Cannabidiol has been put into use under uncontrolled terms to offer therapeutic effects in many occasions thus raising concern on its therapeutic drug monitoring. According to Millar et al (2018), CBD has found a widespread therapeutic application but still there exists lack of data and discrepancies in its pharmacokinetics.⁵² The route of administration of cannabis into the human body system determines the rate by which it is absorbed and its metabolism due to variations in consumed drug concentration.⁵³ Precisely, when tetrahydrocannabinol (THC) is inhaled and assimilates through the pulmonary system, the associated psychotropic effects are manifested within a period of less than 1 minute but reach a maximum after 20 to 30 minutes, but when it is ingested orally, it takes about 30 to 90 minutes for the psychotropic effects to occur approximately reaching a maximum after 2 hours and remain activated in the smoker for 4 to 12 hours depending on the dose smoked.^{11, 53, 54} Cannabis inhalation is characterized by puff numbers, residence time and interval as well as inhalation volume and hold times which greatly influence its bioavailability.⁵⁴ In general, cannabis pharmacokinetics is dependent on smoker related factors in addition to chemical properties of cannabinoids and other compounds present in the smoke.⁴³ Accordingly, smoker related factors embracing age, genetic makeup, renal function and sex which vary from different smoking population across the world, greatly determine the extent to which marijuana pharmacokinetic profiles are expressed.⁵¹

Metabolic activities on THC take place particularly in the liver where microsomal hydroxylation and oxidation processes occur.⁴³ Hydroxylation step involves the conversion of THC into 11-hydroxy-THC under cytochrome P-450 complex enzyme catalysis and subsequently, 11-hydroxy-THC oxidized to 11-nor-9-carboxy-THC which glucuronates to THC-COOH beta glucuronide that lacks psychotropic properties ^{43, 55} as illustrated in Scheme 1, before being excreted though kidneys, faecal matter and urine.⁵²