Cannabis is nature’s gift to mankind to treat various ailments and heal in a natural but effective way. Unfortunately, medical marijuana is still stuck in between the political, legal, and social stigmas – despite the fact that the medical benefits of cannabis have been proven by research studies.
Perhaps intentionally, without looking into the growing body of clinical evidences and widespread legalization of marijuana in various states, the U.S. Drug Enforcement Agency (DEA) still classifies marijuana as a Schedule I drug – the same category as LSD and heroin. Surprisingly, cocaine is listed as a Schedule II drug. DEA classification has five different schedules, with the lowest number having the highest addiction/abuse potential and without any medical benefits, while the highest number has the lowest addiction/abuse potential with potential medicinal benefits.
Based on this listing, it is clear that the DEA considers marijuana to have serious abuse potential and no medicinal benefits, while cocaine has medicinal benefits with comparatively less potential for abuse and side effects. Although cocaine has been used as a topical anesthetic drug for nasal and oral surgeries for years, several other safer, effective and non-addictive alternatives are available.
As cannabis has been classified as a Schedule I drug, it is more difficult to conduct research studies to demonstrate its medical benefits. The purpose of this article is to exhaustively explain the scientific difference between cannabis and poisonous cocaine, and explain how cannabis can safely and effectively treat acute cocaine toxicity.
Don’t Equate Cocaine with Cannabis!
Cocaine is an illicit, psychotomimetic, psychostimulant drug, and it is one of the most abused drugs in the world. Unlike cannabis, cocaine use can cause several moderate to serious health problems such as high blood pressure, abnormal body temperature that interferes with heart functions, arrhythmia, impaired cognitive ability, emotional issues, damage of brain’s reward pathways, and even death. The most notable cocaine toxicity is liver damage (hepatotoxicity) and seizures.
Since cocaine metabolism involves several biochemical reactions and activity on various cellular receptors, developing an antidote for cocaine toxicity remains elusive. Although, several cocaine metabolizers and vaccines have been developed and have demonstrated promising results in the preliminary stages, these research trends have suffered significant barriers from achieving practical or clinical utility in treating acute cocaine toxicity.
A number of clinical trials and experimental studies have demonstrated that acute administration of high doses of cocaine can cause convulsive seizures and severe hepatotoxicity. The exact underlying pathophysiological mechanisms of cocaine toxicity are still unclear. However, it is believed that cocaine can mediate noxious neurological events by blocking dopamine, norepinephrine, and serotonin reuptake in addition to abnormal stimulation of dopamine D2 receptors that can potentially contribute to cocaine-induced seizures. Thankfully, cannabis does not cause convulsive seizures or hepatotoxicity – even at higher doses. So, I can see no good reason to classify cannabis as Schedule I drug.
Excessive cocaine-induced oxidative stress and excessive generation of free radicals followed by inflammatory reactions and cellular necrosis/apoptosis are the hallmarks of hepatotoxicity. These events can be characterized by an abnormal increase in alanine transaminase activity, altered levels of chemokines and pro-inflammatory cytokines, impaired immune system adaptation with characteristic hepatocellular centrilobular focal necrosis in the liver cells. As of now, there is no effective medical management available to mitigate these problems and therefore, mortality is almost inevitable.
To the best of my knowledge, no research studies have reported these side effects after cannabis use. Most of the side effects of cannabis (cannabis-alone use) are mild psychoactive, non-lethal, non-toxic, and temporary in nature. On the other hand, cocaine use – either alone or in combination with other drugs – can cause severe acute hepatotoxicity as a result of hepatocellular necrosis that is often fatal among cocaine abusers.
So, taking the recent medical research evidences into account, it’s pretty easy to understand and argue that cannabis has remarkable medicinal value and it is much safer than other drugs, including cocaine. Actually, marijuana is a hundred times safer than alcohol and cocaine, as reported by a psychologist who performed a decade long research study.
Anti-inflammatory Properties of Cannabis
Let’s look into the anti-inflammatory properties of cannabis and how it mitigates the inflammatory processes of hepatotoxicity associated with cocaine toxicity.
Among other physiological functions, the protective role of the endocannabinoid system (ECS) against noxious stimuli in various tissues including the brain and liver has been proven several times over. ECS comprises of cannabinoid receptors, endocannabinoids, and other metabolic enzymes in the brain, liver, and other peripheral tissues. Endocannabinoids are neuromodulatory lipid mediators of the same cannabinoid receptors that involves in maintenance of optimal health and eliciting marijuana effects. Liver ECS is activated in several hepatic diseases, and depends on the activation of peripheral receptors, particularly CB1 receptors.
Targeting ECS by phytocannabinoids is a clear strategy to achieve great health and to treat several diseases that involve CB1/CB2 receptors.
Cannabidiol (CBD) and tetrahydrocannabinol (THC) are the active principles of cannabis, which possess therapeutic benefits including anti-inflammatory and antioxidant properties that fight against several diseases. When compared to CBD, THC’s use is limited due to its psychoactive properties. CBD acts via multiple pharmacological targets, such as adenosine membrane transporter phospholipase A2, peroxisome proliferator-activator receptor (PPAR), activation of transient receptor potential vanilloid type-1 (TRPV1), the adenosine membrane transporter phospholipase A2, Ca2+ homeostasis, lipoxygenase (LOX) and reducing cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) levels, decreasing the release of TNF-α, 5-hydroxytryptamine receptor subtype 1A (5-H), facilitation of the endocannabinoid system and GPR55. These factors are involved in inflammatory processes, and CBD is believed to elicit its action by influencing these biological mediators and related mechanisms.
One research study has found that CBD effectively treats cocaine-induced hepatotoxicity and seizures in animal models by suppressing inflammatory mediators, and therefore reduces cocaine lethality. CBD restored liver and brain functions via its combined action. However, the same benefit was not observed in other mice that were treated with a fatty acid amide hydrolase (FAAH) inhibitor, which also targets ECS. This result proved that phytocannabinoid is pharmacological in a way not similar to chemical mimetics.
CBD’s anti-inflammatory action involves a plethora of cellular immune response suppressive mechanisms that also inhibit the release of pro-inflammatory cytokines. Another study has reported CBD administration significantly decreased myeloperoxidase activity, leucocyte migration, production of chemokines such as MCP-1 and MIP-2 and proinflammatory cytokines including TNFα and IL-6, which is implicated in inflammatory diseases/disorders including hepatotoxicity.
Acute cocaine hepatotoxicity can occur due to occurrence of hepatic ischemia and/or generation of toxic oxidative metabolites. Cocaine causes powerful hepatic vasoconstriction that can potentially lead to ischemia, reperfusion and injury.
To demonstrate that CBD has the potential to mitigate ischemia/reperfusion injuries of the liver, researchers have conducted a pre-clinical study. The degree of hepatic inflammation was similar to cocaine-induced hepatotoxicity. In the study, experimental animals that were not treated by CBD, hepatic ischemia/reperfusion (I/R) triggered time-dependent increase in hepatic enzyme biomarkers, hepatic oxidative stress biomarkers and associated mitochondrial dysfunction and inflammation were evident and characterized by elevation of TNF-α, macrophage inflammatory protein-1α/2, cycloxygenase-2, intercellular adhesion molecule 1 mRNA levels, nuclear factor κB (NF-κB) activation, p38MAPK and JNK that led to DNA damage and cellular necrosis. These molecular biomarkers are linked with hepatic I/R.
Cannabis has more than 60 different phytochemicals, including THC and CBD, that can scavenge oxidative/nitrative stress-causing chemicals and has the potential to treat several inflammatory processes. CBD treatment significantly suppressed the degree of hepatic inflammation, oxidative stress, and cellular necrosis.
Previous studies also demonstrated that CBD possesses remarkable antioxidant and anti-inflammatory activities against ischemia/reperfusion liver injury in rats. These studies have concluded that CBD down-regulates the molecular pathways of pro-apoptotic mechanisms, suppressing inflammation by inhibiting expression of pro-inflammatory mediators, as well as by scavenging the free radicals that cause oxidative/nitrative stress and cellular damage. Molecular pathological studies have underscored that prevention of oxidative stress generation can have therapeutic advantage in disease processes.
Similar results were echoed in other studies that reported CBD’s hepatoprotective properties, anti-inflammatory action in the liver, and attenuation of hepatotoxicity biomarkers, and cellular damage as a result of liver I/R. It has been shown that CBD pretreatment significantly mitigated hepatic ischemia for 60 min followed by reperfusion for 24 hours. The benefits were evidenced by reversal of hepatic biomarkers. These findings are in accordance with another study that reported hepatic and central benefits of CBD against cocaine toxicity that were characterized by restoration of liver and brain functions in animals.
As this wealth of in-vitro and in-vivo data would suggest, CBD treatment is a novel therapeutic approach against acute cocaine toxicity and related I/R injury.
Anticonvulsant Benefits of Cannabis
Based on the results of the aforementioned studies, it has been confirmed that cocaine toxicity can cause seizures, in addition to the severe liver toxicity. CBD, as a phytocannabinoid, can effectively treats both problems – which can serve as a potential treatment of brain and liver complications of acute cocaine toxicity.
If we look into the molecular mechanisms, phytocannabinods are believed to be the lipid-soluble signaling molecules that can potentially act on both the central and peripheral nervous systems through binding with metabotropic cannabinoid receptors. These receptors are implicated in cellular and synaptic physiology of endogenous lipid signaling mechanisms, particularly the regulation of neuronal excitability.
Epilepsy occurs as a result of altered neuronal excitability, and frequency of seizures can further deteriorate neuronal excitability. As of now, no effective medications are available to completely treat seizures. And the emergence of treatment-resistant seizures appears to be the worst nightmare for seizure patients.
In-vivo and in-vitro studies have shown that CBD can effectively treat cocaine-induced acute seizures, in addition to its anti-inflammatory action in hepatic cells.
Phytocannabinoid CBD exerts anticonvulsant effects and effectively treats pentylenetetrazole-induced seizures in animal models. The anticonvulsant benefit of CBD has been proven against temporal lobe seizures, partial seizures, and electroshock-induced seizures in pre-clinical studies.
While enjoying the anticonvulsant benefits, CBD does not cause sedation, amnesia and other psychotomimetic effects, which is noteworthy in epilepsy treatment. Over the years, cannabinoid treatment was considered as formidably impractical for convulsion treatment due to its psychotomimetic effects. However, this now seems to be possible with CBD treatment.
At this point, we need to extrapolate the results of pre-clinical studies in humans to show CBD’s anticonvulsant potential.
Recently, a clinical trial study has reported that CBD-containing cannabis extract has significantly reduced the seizure frequency in treatment-resistant epileptic children. Although, the cause is unrelated to cocaine toxicity, the anticonvulsant benefit of CBD is applicable for all causes of seizures, regardless of underlying etiology. This study has indicated that CBD can offer a unique advantage in seizure treatment compared with conventional anticonvulsants. This evidence pointed out that phytocannabinoid can activate the CB1 receptors and ECS in the memory-related areas and limits seizure duration.
Adding teeth to the proven health benefits of cannabis, this research evidence shows that cannabidiol possesses hepatoprotective and neuroprotective benefits against cocaine toxicity, which can be used as an effective therapeutic agent in the future in case of a clinical emergency. Additional clinical trials are warranted to further delineate other molecular mechanisms of cannabidiol against cocaine toxicity.
Based on this review, as a scientist, I can see no scientific rationale or plausibility to compare marijuana with illicit drugs such as cocaine and LSD. In short, marijuana provides several medical benefits with mild but tolerable side effects. Meaning, anyone who experiences psychoactivity after cannabis treatment, it’s just temporary, no risk of overdose and non-toxic!
Nevertheless, illicit drugs possess no medicinal value, but cause serious health problems with imminent risk of overdose and related death.