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
3.3 Harms and health impacts arising from consumption of
cannabis
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.
3.4 Application of cannabis as medicine for the management
of Covid-19
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
3.5 Pharmacokinetics of
cannabis
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