6: Cannabis Compounds and
Chemical Addictions

UPDATED date

The most common definition of addiction is that attempted cessation leads to the discovery that stopping is easier said than done. Further evidence of addiction is that use has caused problems severe enough to impair health, work, and personal relationships. Alcoholism, for example, shortens one's life span by 26 years on average[CDC_2022]. It causes one to miss work or be less productive, and it wreaks havoc with family life[Buddy_2021].

Published addiction rates are surprisingly speculative. They are typically given without reference to a definition of addiction and often equate usage rates with addiction rates. There has been research on how street marijuana affects chemical addictions but relatively little research on how specific cannabis compounds affect addictions.

The following sections cover tobacco, alcohol, opioids, cocaine, and marijuana addictions. The topics discussed include mortality, health effects, risk of addiction, and relationship to marijuana. Regarding mortality, the statistics apply to people living nn the United States.

A final section addresses the impact of variations in the gene for the CB1 cannabinoid receptor that is responsible for the intoxicating effects of THC.

6.1 Nicotine and Tobacco  

Mortality. Tobacco kills 1300 people a day[t, Mortality].

Health Effects. Smokers are more prone to develop heart disease, stroke, and lung cancer. They are more prone to cardiovascular diseases, including strokes, heart attacks, and narrowing of blood vessels. COPD is more frequent and more severe in smokers, and the same goes for asthma. Smoking by either men or women adversely affects conception and pregnancy and increases congenital disabilities[t, Health].

Risk of Addiction. There is widespread agreement that nicotine is the most addictive of the commonly used psychoactive drugs. The Nicotine addiction rate is around 32% of those who smoke regularly[t, Addict].

Relationship to Marijuana. Cannabis does contribute to the risk of tobacco addiction. Specifically, cannabis use is associated with increased initiation, persistence, and relapse to cigarette smoking[t, Mj1]. Moreover, tobacco addiction is predictive of marijuana addiction[t, Mj2].

6.2 Alcohol  

Mortality. Alcoholism kills 240 people a day[a, Mortality].

Health Effects. The ill-effects include liver disease, heart disease, hypertension, stroke, and throat cancer[a, Health].

Risk of Addiction. The American Psychiatric Association's DSM-5 uses the term Alcohol Use Disorder (AUD) rather than addiction[a, Addict]. Briefly, AUD is an impaired ability to stop or control alcohol use despite adverse social, occupational, or health consequences[a, nih-aud]. The rate of AUD is thought to be around 10% for men and 5% for women[a, harv-aud].

Relationship to Marijuana. Alcohol consumption increases the effects of THC by increasing THC levels[a, Mj2]. The terpene β-caryophyllene (BCP) and, even more so,  β-caryophyllene oxide (BCPO) may help with alcohol addiction by reducing alcohol consumption[a, BCPO].

6.3 Heroin and Other Opioids  

Mortality. Overdoses kill 130 people a day[h, Mortality].

Health Effects. Long-term use damages the brain's white matter, causes increasingly severe addiction, and damages veins, nasal passages, or lungs depending on the route of administration. It also brings a continuing risk of overdose and death[h, Vertava_2022].

Risk of Addiction. Most opioids are less addictive than tobacco[t, Addict]. Heroin, for example, has an addiction rate of perhaps 23% of  those who use regularly[t, Addict].

Relationship to Marijuana. Legalization of medical marijuana is associated with a decrease in opioid overdoses[h, Chihuri_2019]. CBD may lessen the intensity of heroin relapse triggers[h, CBD]. Methadone patients who regularly use marijuana tend to experience less severe heroin withdrawal symptoms during the initial methadone stabilization phase[h, Mj1]. However, marijuana use may not aid patients in opioid addiction treatment[h, Mj2]

6.4 Cocaine, Amphetamines  

Mortality. Cocaine kills upwards of 40 people a day[c, Mortality].

Health Effects. Long-term use damages the cardiovascular system and creates neurological damage[c, health]. Cocaine, and more especially methamphetamine, damage the mouth, teeth, and nasal passages[c, teeth].

Risk of Addiction. It has an addiction rate of perhaps 17% of regular users[t, Addict].

Relation to Marijuana. Crack withdrawal symptoms are lessened by street marijuana[c, Mj1]. Jamaican women routinely use marijuana to minimize the undesirable effects of crack pipe smoking, specifically paranoia and weight loss[c, Mj2]. CBD and THC can be helpful in extinguishing drug-motivated learned behavior in rats[c, THC].

6.5 Marijuana  

This section is about marijuana and marijuana-based products. The information reported here does not apply to synthetic marijuana products or flavored vape products. In some cases, the effects of marijuana may depend on the route of administration. For example, marijuana behaves differently depending on whether it is smoked or eaten.

Mortality. The conclusion of a 1973 animal study was  that it is not possible to overdose on marijuana or even on THC[m, Thompson_1973][m, Stoner_2021]. Although there are no known examples of fatal marijuana overdoses, potentially fatal complications to existing conditions can result from marijuana use[m, Patel_2020].

Risk of Addiction. Roughly 10% of regular marijuana users become addicted[m, Addict2][t, Addict]. Furthermore, roughly 30% have withdrawal symptoms when quitting. The total number of marijuana users who abuse marijuana or become dependent on it may also be as high as 30%[m, Addict3]. There is evidence that marijuana addiction is easier to kick than alcohol addiction[m, Addict4]. However, marijuana is somewhat cross-addictive with other psychoactive substances[m, Addict5].

People who begin using marijuana before age 18 are four to seven times more likely to become addicted than people who begin as adults[m, Addict6].

Low, subclinical doses of THC have decreased marijuana craving and withdrawal symptoms[m, Addict7]. A clinical trial indicated that CBD reduces marijuana use[m, Addict8].

Health Effects. Therapeutic doses appear to be safe and well-tolerated in adults, including older adults, whether healthy or frail or suffering from dementia. The following paragraphs discuss the possibility of harm to the brain, effect on the lungs, driving impairment, decrease in crime, and improved longevity.

Brain Development. Repeated high doses of THC may interfere with brain development, with long-term adverse consequences. The research results are not easily explained by other variables such as education, wealth, or use of other drugs[m-bd, Brain1][m-bd, Brain2][m-bd, Brain3]. These results are concerning because functional brain development continues until around age 25, and white matter development continues until middle age[m-bd, Brain4]. However, one study shows that heavy marijuana use after age 18 is not associated with significant cognitive decline[m-bd, Brain5]. The interference with brain development begins in utero[m-bd, Brain6].

In addition to overall brain development, there is the related issue of developing psychiatric problems. For most conditions, marijuana seems to help. The main exception is schizophrenia. See the schizophrenia discussion in Psychiatric Conditions.

Effect on Lungs. Smoked marijuana does irritate the lungs and can cause chronic bronchitis. However, it does not significantly increase the risk of major illnesses such as emphysema or lung cancer[ml, Lung1][ml, Lung2]. The following diagram shows that occasional use of marijuana may actually improve lung function[ml, Lung3].

Impact on Driving. The moderate use of marijuana does not affect crash risk when other variables such as alcohol use are accounted for[md, Risk1][md, Risk2]. This is surprising because marijuana impairs neurocognitive performance[md, Impair1] and impairs driving lateral control[md, Impair2]. Possibly, drivers impaired by marijuana know they are impaired and drive accordingly.

Overall, legalization in Colorado has improved people's driving[md, Benefit1][md, Benefit2]. It appears that when other factors such as the prevalence of drunk driving are factored in, marijuana is actually beneficial.

Impact on Longevity. Very little is known on how usage impacts longevity. It is known that marijuana has some adverse effects, such as increased periodontal disease[mlng, Longevity1] and decreased bone mineral density[mlng, Longevity2]. However, there are also some easily recognized positive indications.

Alcohol sales have dropped 12% In states with medical or recreational marijuana laws[mlng, Longevity3]. Along with the decrease in alcohol sales, traffic fatalities have also declined[mlng, Longevity4].

Marijuana legalization has seen a shift away from the use of competing prescription drugs, something that is also likely to affect longevity. The shift is substantial in pain medications but is also significant for medications used to treat anxiety, nausea, seizures, and sleep disorders[mlng, Longevity5].

6.6 Genetic Influence  

This section is rather technical, but it holds the key to who should and should not use THC. It sheds light on why people's responses to THC vary widely, with a few people having severe reactions.

Some of the genetic variation involves the CNR1 gene that codes for the CB1 cannabinoid receptor. That is the receptor responsible for the intoxicating effects of marijuana. Some involves the FAAH gene responsible for breaking down the endocannabinoid anandamide.

Briefly, locations within a gene with genetic variation are called SNPs (single nucleotide polymorphisms). Most SNPs come in pairs, one SNP from each of one's two parents. Typically, each SNP has a major common variant and a minor less common variant. The minor variant tends to be the more problematic of the two, with two copies more problematic than one. Technically, a SNP variant is an allele, and a pair of alleles is a genotype. SNPs have somewhat random names of the form rsxxxxxxx.

Some Background on SNPs

Chromosomes are made up of 'nucleotides' put together in a long double helix. We humans are said to have 23 chromosomes. Actually, chromosomes typically have 23 pairs of coordinating chromosomes. In each coordinating pair, one chromosome comes from the father and one from the mother. Atypically, sperms and eggs actually do have 23 chromosomes.
https://psychologydictionary.org/allele/
https://simple.wikipedia.org/wiki/Allele

The nucleotides in a chromosome are grouped into genes, with a typical gene specifying the creation of a protein. As with chromosomes, genes typically come in coordinating pairs.

A given gene will usually have multiple variants. The easiest to study of these variants are the Single Nucleotide Polymorphisms, or SNPs. A SNP is a nucleotide location in a gene where two gene variants have different nucleotides. The nucleotide variants in a SNP are referred to as alleles. The CNR1 gene is known to have at least 22 SNPs
https://www.frontiersin.org/articles/10.3389/fgene.2018.00199/full.

Surprisingly, only four nucleotides are used to build genes and chromosomes. They have interesting names that are always abbreviated to the letters T, C, G, or A. Usually, one allele will occur more frequently than the other. The more common allele is referred to as the major and the less common one as the minor allele. However, for some SNPs one allele will be the major allele in one ethnic group and tthe minor allele in another; in such cases the over all major/minor distinction reflects the estimated average over all collected samples.

As with genes and chromosomes, SNPs come in pairs. So, for example, a SNP with T and C variants leads to four genotypes: (T,T), (T,S), (S,T) and (S,S). But (S,T) is functionally equivalent to (T,S), so (S,T) is merged into the (T,S) genotype, leaving only three genotypes.

Sometimes, it is necessary to look at a group of several alleles spread across one or more genes to understand how they relate to a given medical condition. Such groups are typically inherited together from a single parent and are referred to as haplotypes. Haplotypes are typically listed as alleles separated by hyphens, for example, C-G -A.

Finally, there is the matter of how SNPs are named. Initially, each research group had its own naming conventions, an approach that soon devolved into utter chaos. So the National Center for Biotechnology Information (NCBI) started a registry where scientists can submit a SNP, and the SNP will be assigned a unique name. NCBI refers to their registry as a reference sequence. A SNP's NCBI name always consists the letters "rs" (for "reference sequence") followed by the SNP's registration number, for example, rs2023239. So when someone refers to the rs2023239 SNP, others can know exactly which SNP they're talking about. https://www.ncbi.nlm.nih.gov/refseq/about/
In introducing a SNP, we will specify its gene, its name, and it's major and minor alleles, like so: rs2023239, T>C.

The conventions introduced in this section are found in Wikipedia and various authoritative sources. However, they do not reflect universal practice.

† All of the research reported in this section is qualitative. SNPedia's SNP catalogue has proved invaluable in constructing the following overview

rs2023239

This SNP is on the gene that codes for the CB1 cannabinoid receptor. The minor rs2023239 allele is named C for cytosine. Possession of the C allele flies in the face of the nearly universal impression that marijuana has a mellowing effect. In a study published in 2019, C allele carriers who received THC experienced more anger and hostility than those who received a placebo[gi, CNR1-anger].

Those with the C allele also experience stronger cravings while using marijuana and have greater withdrawal symptoms in response to abstinence[gi, CNR1-craving].

A study of patients with alcohol dependence linked the minor C allele with greater subjective reward from alcohol as well as greater alcohol consumption[gi, CNR1-alcohol]

rs324420

This SNP is on the gene that codes for the FAAH enzyme, which breaks down anandamide. The minor rs324420 allele is named A for adenine. It results in less of the FAAH enzyme, causing higher anandamide levels. Anandamide is correlated with happiness[gi, FAAH-Happiness]. Unfortunately, the minor A allele also carries an increased risk for substance use disorder[gi, FAAH-addiction].



The references are rendered according to the Citations Online architecture. Their format is designed exclusively to meet the needs of the web[Williams_2022]. The reference icons are from Freepik - Flaticon[Freepik].

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icon icons/dna.png. gi. Marijuana: Genetic Influence.

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