Historical acts and facts that have influenced cannabis legislation

1906 Federal Food and Drug Act

              The Federal Food and Drug Act was the first time the government started controlling the regulation of food and drugs (including any medicines that contained such items as cannabis). It was meant to oversee the branding, packaging, and risk of contamination of these items.  This Act did not outlaw or tax any products, but rather it was just the beginning step of government regulation of consumed products.  It expanded the government’s reach to cannabis, since cannabis was on the USP-NF list of drugs.  This act also paved the way for the governments to enact the Opium Act, which banned opium for the first time.  This government regulation would soon spread to other drugs, including cannabis.

1914 Harrison Act

              The Harrison Act of 1914 saw the registration of prescription recommendations by doctors.  This was also the first time that the government began taxing medicinal drugs.  These taxes, however, were used more to direct the behavior of Americans rather than just raise revenue.  The government was imposing drug regulation, not through criminalization, but rather through taxation (such as high taxes on cigarettes today).  If taxes were high enough in products that contained cannabis, people would be discouraged from using them.  This also raised revenue for the government.  While this is the first time that the government is seen directly trying to influence drug use behavior, it is just the beginning of the strict regulation and enforcement that would soon follow.

1930 Anslinger takes control of Bureau of Narcotics

              In 1930, Harry Anslinger took over control of the Bureau of Narcotics. Anslinger was an outspoken and staunch supporter of all things prohibition.  In fact, he was still an advocate of alcohol prohibition even after it was repealed.  His legacy, until he left his office in 1962, would, again, be prohibition no matter how the scientific and social data refuted his beliefs. He gave speeches and rallies all over the United States to groups about the horrors of cannabis and how the drug should be loathed.  He brought about the “reefer madness” era in which he touted that cannabis would turn ordinary people into rapists and murderers. He made comparisons between alcohol and cannabis, saying that they would ruin society and the moral compass of Americans.  He even went so far as to manipulate data and skew anecdotal evidence to support his crusade.  His zealous battle over cannabis also stepped from deeply seated racism – against minority communities in the United States as well as immigrant populations, especially from Mexico.  His ardent campaigning led to the Marijuana Tax Act of 1937 that was the first effort to criminalize the cannabis trade.  His lasting legacy is seen to this day in the federal criminalization of cannabis and its place on the Schedule I drug list, touted as a substance with no medical viability.

Understanding decriminalization vs legalization

Understanding the terms decriminalization and legalization is vital to learning about the current state of cannabis law.  Some might think that the words are interchangeable, but alas, they are not.  Decriminalizing cannabis means that there are no longer felonies and misdemeanors associated with the drug.  Rather, a fine is usually imposed by law enforcement.  Legalization, on the other hand, means that cannabis is free to be used by the general public.

Decriminalization of cannabis is an important step to the full legalization.  States may lean toward decriminalization as opposed to legalization because it starts to bring the penalties, and therefore costs, down for cannabis crime.  Currently, twenty-seven states and Washington DC have decriminalized cannabis.  The costs for arresting and prosecuting those who commit cannabis crimes is astronomical. Decriminalization helps reduce these costs as well as reduce incarceration for nonviolent cannabis offenders.  

Legalization of cannabis is the acceptance of it into mainstream society.  This means that there are no penalties for cannabis use.   Cannabis would be removed from Schedule I of the Controlled Substances Act and would be available for widespread use. As well, it could be regulated at the federal level, taxed for government income, and backed by insurance companies and banks. Research could be done freely with cannabis availability. Legalization would not mean the end of medical use.  Medical cannabis would be available everywhere.  This means that every state or the federal government would need to create a regulatory framework for medical marijuana separately from recreational.  Medical cannabis needs to be prescribed through doctors according to a treatment plan, not just bought at the corner dispensary.

Some states have already legalized recreational cannabis and many others have decriminalized it.  Decriminalization reduces the costs of everything associated with illegal cannabis (prosecution, incarceration).  Legalization means that both recreational and medical cannabis no longer have any penalties, federally or statewide.  Medical marijuana will have to be treated as a separate entity from recreational, as it is necessary to have a physician and plan to oversee treatment.

Heavy metals in cannabis

In 1986, following the tragedy at Chernobyl nuclear power plant, industrial hemp was planted in order to help clean heavy metals and radioactive elements that had seeped into the ground. The cannabis plant, known for being a hyper-accumulator of heavy metals as well as pesticides, can seep up contaminants where other methods fail.1 While this is a boon to contaminated environmental sites, it poses a risk to both recreational and medical cannabis users, as contaminants can be extremely toxic to humans.2 These contaminants include such heavy metal as lead, arsenic, cadmium, and mercury, and pesticides such as bifenthrin, and diaxinon.4 As well, due to lack of federal regulation of the burgeoning cannabis market, these contaminants can occur at many points along the growth and processing cycles. Therefore, it is important to the know the contaminants and heavy metal content of cannabis products, as unlike pharmaceuticals, there is rarely a maximum daily dose set.

              The amalgamation of pesticides and heavy metals occurs in cannabis because of its phytoremediation properties.  Industrial hemp is often used for cleaning environmental sites. Cannabis moves water and nutrients through its roots and plant through a process called transpiration.3 As the stomata open to release water to evaporate, negative pressure creates a vacuum that pulls more water and nutrients in the plant. This is what also causes the cannabis plant to soak up many heavy metals.3 Unfortunately, there are many ways that cannabis can leech contamination during processing and growing. First, as mentioned above, is the natural environment in which the cannabis is planted. Soil can contain contaminants from years before that only cannabis can draw out of the ground.  It is extremely important to have a soil analysis done prior to picking a growing site. Prior agricultural sites may often have the presence of fertilizers and pesticides that may not have affected past crops but can greatly affect cannabis. Unfortunately, because of illegal status of cannabis federally, there are not standard pesticides recommended for growing cannabis.

Other contamination can occur also during testing and processing. Some organic solvents that are used in laboratories may pose health hazards to the medical cannabis community. Solvents like butane, ethanol, and benzene are used to test and process cannabis, but they do pose neurotoxic and carcinogenic risks as well.4 Labs, however, also test for contaminants. For heavy metals, scientists use inductively coupled plasma mass spectrometry (ICP-MS) to detect, at the very least, cadmium, arsenic, lead, and mercury.5 Again, due to the status of cannabis as a Schedule I drug, there is no federal standardization among testing requirements.  States must decide what exactly what requirements should be in place for testing. Unfortunately, this leads to many states doing less testing than what may be needed to keep patients safe.

The main reason for the necessity of testing is to keep toxic levels of contaminants to a minimum to protect the health of the cannabis patient.  While it is important to eliminate the use of pesticides such as chlorpyrifos and methamidophos in cannabis agricultural, it as important, if not more, to minimize heavy metal consumption. Lead poisoning can cause dizziness, muscle pain, and gastrointestinal issues. Cadmium poisoning can lead to cancerous tumors. Mercury poisoning can cause extensive neurological damage. Arsenic is also extremely toxic as well as carcinogenic.5 Different states have different regulations on the levels of numerous contaminants that can exist in cannabis.  Unfortunately, some of those states do not consider some sources of contamination and may miss when toxic levels are present in products.  As well, unlike regular pharmaceuticals, cannabis users tend not to check levels of contaminants in the number of products they use.  With regular heavy use of cannabis, whether smoking, vaping, applying topical products, or using oral products, it easier to exceed toxic levels of contaminants as cannabis doses tend to be more in a range, rather than a maximum dose.  It is up to the federal government, when cannabis is legalized, to set standards for pesticides and all heavy metals that could pose any risk to the cannabis community.  Although states where medical cannabis is legal do testing for contaminants, the collective knowledge of all states can help further develop better standards, processes, and testing for the cannabis industry.

References

  1. Thomas R. Regulating heavy metals in cannabis: what can be learned from the pharmaceutical industry? Part 1. Analytical Cannabis website. https://www.analyticalcannabis.com/articles/regulating-heavy-metals-in-cannabis-part-i-what-can-be-learned-from-the-pharmaceutical-industry-312336. Accessed on November 29, 2020.
  2. Jaishankar M, Tseten T, Anbalagan N, Mathew BB, Beeregowda KN. Toxicity, mechanism and health effects of some heavy metals. Interdiscip Toxicol. 2014;7(2):60-72.
  3. Thomas R. Regulating heavy metals in cannabis: what can be learned from the pharmaceutical industry? Part 2. Accessed on November 29, 2020.
  4. Pizzorno J. What Should We Tell Our Patients About Marijuana (Cannabis indica and Cannabis sativa)?. Integr Med (Encinitas). 2016;15(6):8-12.
  5. Kariuki L. Heavy metals in cannabis: important things to know. Extraction Magazine website. https://extractionmagazine.com/2020/04/04/heavy-metals-in-cannabis-important-things-to-know. Accessed December 1, 2020.

Pharmacokinetics and pharmacodynamics of THCA

Tetrahydrocannabinolic acid (THCA) is a cannabinoid produced by the cannabis flower.  It is a relatively unstable compound that is easily decarboxylated by heat.  While it does not have any psychoactive properties itself, when decarboxylated, it forms into tetrahydrocannabinol (THC), the psychoactive component of cannabis.  THCA may play an important role in the treatment of neurological issues such as neurodegenerative and neuroinflammatory disease.1

              THCA in the precursor to THC.  THCA is found in the raw flowers of the cannabis plant but can be easily converted into THC by heating or baking the flower.  Heat, however, is not the only method of decarboxylation. Age and light cause decarboxylation as well.2 Because of this, THCA is notoriously unstable and hard to research.  With mice, THCA in an oil carrier shows a very short half-life time of 67 minutes.3 In humans, the half-life after an oral dose is closer to 3.4 hours.1 THCA cannot be vaporized or smoked, as the heat causes its transformation into THC.  In a study of mice, researchers injected an oil and THCA mixture to several subjects.  They found that THCA peaks quickly in the plasma and slowly tapers off over about 2 hours.3  The Cmax from a 10 mg/kg solution was approximately 2.8 µm/ml.2 The presence of the THCA in plasma as well as the brain shows that while difficult, THCA can be isolated and given in a manner where it does not carboxylate.

              The rapid decarboxylation of THCA into THC makes it extremely difficult to see the mechanisms of THCA inside the body. Research has shown that THCA has little affinity for the CB1 and CB2 receptors.1 Upon initial consumption of THCA and THC by a heat source, it appears as though their concentrations are similar but then rapidly diverge.  The THCA is almost all converted to THC3.  THC has a partial affinity for CB1 and CB2 receptors and causes the psychoactive effect of cannabis.  While THCA does not bind readily to the endocannabinoid system receptors, it does have an affinity for PPARƴ receptors.1 PPARƴ receptors involve insulin sensitivity as well as glucose metabolism.  In general, PPARƴ play a major role in homeostasis of energy and metabolic function.4 Because of the affinity for these particular receptors, THCA may play an important role in several different bodily functions. In fact, THCA has shown to high neuroprotective activity.1 This means that THCA can have a positive effect on neurodegenerative diseases like Parkinson’s or Alzheimer’s.  It may also have a positive effect of neuroinflammatory diseases such as Multiple Sclerosis. THCA has also been seen to have anti-inflammatory properties to treat arthritis and lupus as well as anti-emetic properties to combat nausea and appetite loss.5

              THCA is a precursor to the psychoactive cannabinoid THC.  It is hard to isolate THCA as it decarboxylates into THC by heat, age, and light.  If isolated and taken, THCA has a similar Cmax curve as THC – it starts with high concentration in the plasma and slowly tapers off. THCA, unlike THC, has little affinity for CB1 and CB2. It does, however, has affinity for PPARƴ receptors that help regulate homeostasis of the body.  Because of this, THCA may have positive effects on neurological diseases as well as anti-inflammatory effects on arthritis and anti-emetic properties.

References:

  1. Eddington N. Metabolism of active and non-active agents of the cannabis plant. MCST608 Lecture Slides. University of Maryland School of Pharmacy.
  2. McPartland JM, MacDonald C, Young M, Grant PS, Furkert DP, Glass M. Affinity and Efficacy Studies of Tetrahydrocannabinolic Acid A at Cannabinoid Receptor Types One and Two. Cannabis Cannabinoid Res. 2017;2(1):87-95.
  3. Lyndsey L, Anderson IK, Low SD. Banister IS, McGregor, Jonathon CA. Pharmacokinetics of Phytocannabinoid Acids and Anticonvulsant Effect of Cannabidiolic Acid in a Mouse Model of Dravet Syndrome. Journal of Natural Products. 2019;82(11):3047-3055.
  4. Tyagi S, Gupta P, Saini AS, Kaushal C, Sharma S. The peroxisome proliferator-activated receptor: A family of nuclear receptors role in various diseases. J Adv Pharm Technol Res. 2011;2(4):236-240.
  5. What is THCA and what are the benefits of this cannabinoid? Leafly.com website. Accessed on July 12, 2020.

Analytical vs preparative chromatography in cannabis processing

Chromatography is a method of separating mixtures in a laboratory setting using two distinct phases, a mobile phase and a stationary phase.  While analytical chromatography helps gather specific information on the compounds in a mixture, preparative chromatography isolates and purifies the sample.1 In the cannabis industry, both analytical and preparative chromatography are important for the identification and production cannabis products.  Both types of chromatography are complementary. Not only do the methods ensure the compounds are correctly identified, but they also ensure that final products are safe and effective, as well as labeled accordingly.2

The basic process of chromatography is simple. It occurs when a mixture is dissolved in a fluid, which can be liquid or gas, and is then passed through another material, usually solid.  The fluid, or mobile phase, interacts with the solid, or stationary phase.  During this interaction, the mobile phase separates into components as it travels through the stationary phase.1 There are many types of different chromatography that take advantage of the properties of the mobile and stationary phases to separate and/or identify a substance. Liquid or gas chromatography change the physical state of the mobile phase. Column or planar chromatography changes the shape of the stationary phase. Ion-exchange and size exclusion chromatography also chance the actual mechanism of separation. Chromatography is a powerful tool available to scientists to identify and purify mixtures.

Chromatography can either be used to identify or purify a mixture. In fact, most often, chromatography is used for both, isolating and purifying specific compounds for further research or commercial purposes. The process of identifying and analyzing compounds is analytical chromatography. In this type of analysis, the goal is to separate as many peaks as possible, using a baseline to help identify components of a mixture. For instance, in analytical HPLC, the sample volume is usually small, around 1 – 20 µl, as identification is the primary purpose.3 The column is small, only 1-4mm in diameter, and the flow rate is low, typically 1.0 mL/min. Detection is set up to be as sensitive as possible.  As well, there are no fraction collections or solvent recovery, as the mixture is just being analyzed, not collected.3 On the other hand, preparative chromatography isolates and purifies specific compounds to collect and form a substantial sample of the desired product. Therefore, with preparative chromatography, recovery is most important rather than identification.  For instance, in HPLC, the separation goal is to see the one desired peak.  The sample volume is as large as possible, to maximize collection while minimizing contamination or peak overlap.3 The column diameter is usually larger than analytical techniques, greater than 4mm. The flow rate is also higher, around 5 – 5000 mL/min, as volume is more desired for this preparation.3 Mostly importantly, the solvents and eluents are collected in preparative chromatography, as the end goal is to collect a purified specific substance from the column.2

Both analytical and preparative chromatography are extremely important to the budding cannabis industry.  One of the biggest concerns in the industry today is the accurate inclusion and reporting of cannabinoids and other cannabis compounds, such as terpenes, in medical and recreational commercial products. Analytical chromatography is used to identify the various components of a sample of cannabis.  A sample of cannabis plant material can have thousands of different compounds in it, including over 110 active cannabinoids.  THC and CBD are among the most commonly identified and used cannabis components.  Analytical chromatography can identify the THC and CBD in a sample as well as the other components as well.  Initial cannabis samples can be tested for the presence of illegal pesticides.4 As well, cannabis can be tested for the presence of illicit substances in their formulations. Also of importance, because chromatography is not heat dependent, cannabinoids and other cannabis components can be accurately identified by analytical chromatography, as decarboxylation or destruction by temperature is avoided.5 Preparative chromatography allows for these components to be separated out of the plant slurry and be refined.  In HPLC, silica resin columns are popular to use with lipophilic cannabis compounds. Cannabinoids are easily separated from the rest of the plant material using this process.2 Unfortunately, stationary columns are expensive and run times are long, so scientists are exploring other types of preparative chromatography for cannabinoids such as centrifugal partition chromatography purification.2

Analytical and preparative chromatography use the same techniques of separating mixtures using a mobile phase and a stationary phase.  While analytical chromatography strives to qualitatively identify mixtures, preparative chromatography strives to separate mixtures.  In the cannabis industry, the analytical technique identifies cannabinoids as well as the many other components of the cannabis plant.  It can also identify contaminants, pesticides, or other illicit chemicals. Preparative chromatography can separate and collect cannabis components, such as the desirable compounds THC and CBD. It may, however, become expensive, based on column and solvent costs. In the big picture, the two different techniques of analytical and preparative chromatography, however, will remain complementary – one technique to identify and one technique to purify, especially in the cannabis industry.

References:

  1. Analytical and Preparative Chromatography. News Medical Life Sciences website. https://www.news-medical.net/life-sciences/Analytical-and-Preparative-Chromatography.aspx#:~:text=In%20analytical%20chromatography%20the%20purpose,the%20components%20of%20the%20sample.&text=The%20purpose%20of%20preparative%20chromatography,specific%20substance%20from%20the%20sample. Accessed on October 28, 2020.
  2. HPLC vs CPC for cannabis testing. Gilson website. https://www.gilson.com/default/hplc-vs-cpc-for-cannabis-testing. Accessed on October 28, 2020.
  3. What is the difference between analytical and preparative HPLC? Knauer website. https://www.knauer.net/en/what-is-the-difference-between-analytical-and-preparative-hplc/f24135. Accessed on October 28, 2020.
  4. Advancing chromatography methods for cannabis analysis. Cannabis Science and Technology website. https://www.cannabissciencetech.com/view/advancing-chromatography-methods-cannabis-analysis. October 28. 2020.
  5. Determination of cannabinoids with analytical HPLC. https://www.knauer.net/en/Blog/Determination-of-Cannabinoids-with-Analytical-HPLC. Accessed October 28, 2020.

Cannabis and the necessity for USP standards

The United States Pharmacopeia (USP) is a non-profit, non-governmental organization that provides official standards for identity, strength, quality, and purity in medicines. As well, they also produce standards for food ingredients and dietary supplements.1 For medicine, food, and dietary supplements, the USP publishes reference standards to ensure accuracy and reproducibility of laboratory procedures. For cannabis, the USP has published a scientific paper on cannabis standards to help provide safety and accuracy to the cannabis community.2 They have not, however, published a USP monograph to officially record these findings, as the US government still does not recognize cannabis as a legal medical product. The need for standards is extremely important for the safety of consumers as well as to protect the growers, processors, and other parts on the cannabis production industry.

              The first and foremost reason that the cannabis industry needs USP reference standards is the question of safety.  USP standards are enforced by the FDA. Again, because cannabis is still on the Schedule I drug list and therefore federally illegal, the FDA does not recognize it as a type of medicine or supplement. In fact, there are actually no monographs or general chapters produced by the USP on cannabis for laboratories to follow.3 Instead, they have published a scientific paper to help get the references standards out to the laboratories that need them. The USP’s recommendation includes standardizing methods and attributes for the ensured quality of a cannabis product.4 This standardization is vital to a cannabis product that is properly labeled and free of any contaminants.  Unfortunately, with cannabis, it is difficult to produce homogenous and identical plants from the same grower, let alone from multiple locations throughout the globe. The content of the plants will be different, including THC and CBD potency, as well as terpene content. The need for a standard way of testing these differences is vital for the growth of the cannabis industry.

With a USP reference standard, labs can standardize their procedures for identifying and quantitating the important compounds and contaminants in cannabis. For instance, the mold, Aspergillus fumigatus, can survive in the cannabis flower after smoking and vaporization. If inhaled, Aspergillus can cause serious damage to the lungs and can also be fatal in patients with compromised immune systems.2 Unfortunately, there is no decent test for Aspergillus. The USP must work with other international standards group to help formulate a standardized test which can then be distributed to the cannabis industry for use with identification and purification.2 Along with microbial contamination, formulation processes and adulteration could add contaminants to the cannabis flower.5 The USP can help by providing lists of materials that are safe for cannabis processing.

With USP standards in place, there would be little question about lab techniques and procedures, therefore, in theory, every lab could produce similar results for the same sample.  By having labs work with the same standards, potencies should be the most accurate, as they can be calculated by multiple labs.  This would also discourage “lab shopping” in which cannabis processors use different labs to create the outcome they want instead of the actual reproducible scientific results. “Lab shopping” has been a particular problem in the industry, as cannabinoid potency can be labeled at something significantly different than the product actually has. It is important to know the cannabinoid and terpene contents of cannabis in order to produce the most reliable medicine. Quantification of cannabinoids is also extremely important to the legality of hemp as well.  If a grower’s hemp tests above 0.3%, it is no longer hemp, but rather psychoactive cannabis that could lead to significant legal problems in the future.

Using their experience with other botanical products, the USP has published guidelines for the identification and quantification of the components of cannabis.4 While not an official monograph, the cannabis standards are extremely important for labs to follow in order to ensure accuracy of identification and quantification. Unfortunately, because of the federal status of cannabis, the USP’s hands are somewhat tied in producing and enforcing standards. Labs can have bad techniques, wrong materials, or sometimes even malicious intent which can badly skew the results of cannabis analysis. The FDA usually enforces the USP standards, but the FDA has only approved monographs for dronabinol, a synthetic form of THC, that is the only FDA approved medication associated with cannabis.4 More standards and monographs need to be developed, as the reliability of a lab’s ability to refine, purify, analyze, identify, and quantify cannabis can be seriously compromised.

References

  1. Supporting the quality of cannabis for medical use. USP website. https://www.usp.org/dietary-supplements-herbal-medicines/cannabis. Accessed on November 22, 2020.
  2. Cannabis for medical use: consistent quality to help protect patients. USP website. https://www.usp.org/dietary-supplements-herbal-medicines/cannabis. Accessed on November 22, 2020.
  3. Everything old is new again: cannabis returns to USP. Cannabis Science and Technology website. https://www.cannabissciencetech.com/view/everything-old-new-again-cannabis-returns-usp. Accessed on November 22, 2020.
  4. Cannabis for medical use FAQ. USP website. https://www.usp.org/sites/default/files/usp/document/our-work/DS/Cannabis_FAQ.pdf. Accessed on November 22, 2020.
  5. Giancaspro GI, Kim NC, Venema J, et al. The Advisability and Feasibility of Developing USP Standards for Medical Cannabis. In Pharmacopeial Forum 2016;42(1).

THC vs. CBD for pain

              For thousands of years, cannabis has been used as a medical treatment for a variety of ailments, pain relief being one of the most common reasons. In the medical community, the use of cannabis for pain relief is studied by scientists, not only to understand the mechanisms of the components of cannabis, but also to provide the most safe and effective treatment for various types of pain including analgesic and neuropathic. While in recent studies, both tetrahydrocannabinol (THC) and cannabidiol (CBD) have shown pain relieving properties individually, the entourage effect has seemed to show that a combination of the components of cannabis, including THC and CBD, may be the answer to various types of pain relief.1

              When scientists discovered the endocannabinoid system, they also began to understand how CB1 and CB2 receptors regulate various internal processes, including immune function, appetite and digestion, inflammation, cognition, and behavior.1 Endocannabinoids are produced in the body, however phytocannabinoids, such as THC and CBD, are found in cannabis and hemp in varying concentrations.  THC is a partial agonist for CB1 receptors found mainly in the central nervous system that produces the psychoactive properties of cannabis.  It is also a partial agonist for CB2 receptors found elsewhere in the body, including the immune system.1   CBD can act as an antagonist for endocannabinoid receptors, but is also  an endocannabinoid modulator.1  Both THC and CBD concentrations in the body are dependent of method of administrations, with inhaling producing a shorter response time and half-life, while oral ingestion leads to first pass metabolism and production of metabolites that are longer lived.2

              In scientific studies, both THC and CBD have been seen to have pain relief properties, specifically analgesic and neuropathic.  The mechanisms by which CBD works in the body is largely unknown.  It can be a modulator of opioid receptors, which in turn can make it an analgesic.3 As well, CBD interacts with PPAR-gamma, a protein associated with anti-inflammatory properties.  The CBD and PPAR-gamma interactions may increase anti-inflammatory responses.3 On the other hand, THC is an agonist for CB1 and CB2 receptors.  CB1 activation in the endocannabinoid system is associated with a reduction in pain and inflammation.2 THC is also seen to have 20x the anti-inflammatory properties of aspirin and approximately two times that of hydrocortisone.3  THC works in various ways to produce pain relief, including its interaction with serotonergic, glutamatergic, and the endorphin and enkephalin systems.3 All of these interactions make THC an extremely effective pain relief option.

              The choice between CBD or THC for pain relief depends on two main issues – availability and effectiveness.  While CBD is widely spread available, the acquisition of THC is much more difficult, depending on individual state rules.  Perhaps the most important, though, is whether CBD or THC is more effective.  Because of a lack of research, effectiveness, especially in CBD, is based on anecdotal evidence. It is apparent, however, that the entourage effect allows a combination of THC and CBD to be the most effective for pain relief.  The entourage effect is the synergy of all the components of cannabis.  THC, CBD, terpenes, and flavonoids, along with the hundreds of other compounds found in cannabis, work together by different mechanisms to seemingly produce the greatest pain relief in a variety of circumstances, including neuropathic pain and hyperalgesia. Therefore, the answer to whether CBD or THC is better for these types of pain is not specifically clear.  Both research and anecdotal evidence has consistently shown that the combination of compounds in cannabis is perhaps the best pain relief option.1,2

              The major cannabinoids in cannabis, THC and CBD, both display pain relieving properties individually.  While the mechanism for CBD is not completely understood, it does seem to reduce chronic pain.  As well, THC works on various system to produce pain relief.  The question of which compound produces the best pain relief does not have a simple answer. In fact, the combinations of all the compounds in cannabis, including THC and CBD produce the best synergistic effect of pain relief.  The entourage effect, which includes other compounds like terpenes and flavonoids, shows that the whole plant may be the most effective in combatting both neuropathic pain, hyperalgesia, and inflammation.

  1. Mallick-Searle T, St. Marie B. Cannabinoids in Pain Treatment: An Overview. Pain Management Nursing. 2019;20(2):107-112.
  2. Russo EB. Cannabinoids in the management of difficult to treat pain. Ther Clin Risk Manag. 2008;4(1):245–259.
  3. WHO Expert Committee on Drug Dependence. World Health Organization. Cannabidiol (CBD). https://www.who.int/medicines/access/controlled-substances/5.2_CBD.pdf. Accessed November 16, 2019.

An antidote for cannabis intoxication

The use of “antidotes” or drugs that reverse the action of another drug are very familiar to the public today as the opioid crisis continues to grow.  Naloxone, otherwise known as Narcan, is the most commonly known drug to treat opioid overdoses. Like Narcan for heroin, rimonabant is an antidote for cannabis intoxication. Most people are not familiar with the concept of cannabis intoxication. While there is little to no chance of death, there are symptoms, such as anxiety, that cause numerous number of emergency room visits a year.1 Scientist have worked a treatment for this intoxication, rimonabant, but unfortunately, the mental health side effects have caused it to be unacceptable for patient use.2

              As more and more states and countries are legalizing both medical and recreational cannabis, the instance of intoxication cases have increased as well.  For example, when Colorado legalized recreational cannabis, cases of intoxication increased to almost twice the rate of the rest of the United States, about 6 per 100,000 people.3 The average user may think it is impossible to overdose on cannabis like heroin or other opioids.  While cannabis intoxication is not known to be deadly, it does exist, and emergency room cases are not uncommon.  The most prevalent symptom of the intoxication is severe anxiety.  Other symptoms can range from confusion and paranoia to a rapid heartbeat and hallucinations.3 Currently there is no standardized dosing method for the various strains of cannabis. Without dosing, intoxication is possible, especially in edibles, as the effects take longer to manifest and lasts longer.3  

              Benzodiazepines and sedatives are the usual treatment for cannabis intoxication in the ER.  Unfortunately, these medicines can increase the sedative effects of cannabis.1 An alternative to these treatments exists and actually works very well as an antidote to cannabis intoxication.  Rimonabant, the generic name of Acomplia, is a CB1 endocannabinoid receptor antagonist.2 It was designed to be an anti-obesity drug. In the body, CB1 and CB2 receptors are G-protein linked receptors of the endocannabinoid system.  CB1 is found in the central nervous system while CB2 is found in the immune system.  These receptors normally bind to endocannabinoids found naturally in the body.  When cannabis is ingested, THC binds to the CB1 receptor to cause psychoactive effects.1 Rimonabant is a CB1 antagonist.  This means that it binds to the CB1 receptor, kicking off the bound THC is the process.  Being an antagonist, it deactivates the receptor.1    

              Looking purely at the antagonist activity, rimonbant is an excellent antidote to cannabis intoxication.  It reverses the symptoms without the lethargy of benzodiazepines or sedatives.  Unfortunately, the drug has severe mental health implications.  Suicidal tendencies and depression were rampant among patients taking rimonbant.4 In 2006, Europe approved it for weight reduction.2 In 2007, the FDA recommended against approval due to the serious side effects. The equivalent agency in Europe, the European Medicines Agency, withdrew the drug from production in 2009 for the same reasons.  Today, rimonabant is no longer produced or used in Europe or the US.4         

              Since the legalization of cannabis has started to become widespread, instances of cannabis intoxication have increased as well.  Emergency room doctors commonly use benzodiazepines and sedatives to treat symptoms such as anxiety, paranoia, and hallucinations but these treatments tend to exacerbate the drowsiness associated with cannabis use.  Rimonabant, a CB1 antagonist initially created to fight obesity, can replace THC on the CB1 receptor and counteract the THC psychoactive effects.  While rimonabant was very effective in weight loss and reversing cannabis intoxication, its side effects had significant impacts on mental health in patients including suicidal tendencies and major depression.  Accordingly, the FDA and European equivalent banned its use.  Therefore, while an effective antidote to cannabis intoxication does exist, its side effects prevent it from being used by the medical community.

  1. Cannabis Overconsumption – Current and Future Treatments website. https://profofpot.com/treatment-cannabis-overdose. Accessed on November 10, 2019.

Classifying cannabis strains

The current classifications of cannabis rely on morphologic traits or chemical characteristics.  These classifications can be very confusing, especially in with the vast amount of hybridization that has occurred in the cannabis place over the last century.  A typical user will classify the various strains as “sativa” or “indica” when in fact they could be both C. indica strains.  As well, a plant that appears to be a C. sativa strain, with long thin leaves, may be in fact a hybrid. For these reasons, chemical characteristics are much more valuable to use when classifying the different types of cannabis.

              Morphological classification of cannabis consists of grouping cannabis by their physical traits.  The C. sativa is thought to originate from the spread of plants from Asia and the Himalayas down to northern Africa.2 This strain tends to have lighter green leaves that are longer and thinner in order to adapt to hotter environments.  C. sativa is usually seen to be taller and have a sparse number of flowers.1 It is the primary strain used in industrial hemp. The origins of C. indica are thought to be from the spread of plants near central Africa, Afghanistan, and China.  These were also the plants that eventually spread to Latin America.2 C. indica strains tend to have a bushier appearance. The leaves are shorter and broader than those of the C. sativa strain.3  While classifications based on phenotypes such as these seem straightforward, the dioecious nature of cannabis causes hybridization among strains easily.2 What was once classified as a C. sativa may contain high amounts of THC and find genetic links to C. indica ancestors.  For this reason, classification by chemical characteristics is much more accurate.4

              Hybridization among the different strains of cannabis has been happening ever since it has been used and cultivated by humans.  By crossing male and female plants of different strains, the desirable chemical traits, such as plants high in THC, are easy to create.  In fact, most strains that are found in the medicinal market are a hybrid of C. sativa and C. indica.  These chemical differences make it almost impossible to classify by phenotype alone.4 Instead. The current and most accurate ranking system follows a numeric system.  Type 1 cannabis plants are high in THC and low in CBD.  Type 3 plants are high in CBD and low in THC. Type 3 plants are a combination that show different THC:CBD ratios.4 Using this classification, a pure C. sativa would fall into type 3 while a C. indica would be a type 1.  Hybrids of the two types would be a type 2.4 This is a much more accurate way of classification because the actual chemical constituents show what strain may or may not be dominate in a certain plant based on THC:CBD ratios.

              The original strains of cannabis plants, C. sativa and C. indica, have been so vastly hybridized that classifying a single plant by its physical appearance is nearly impossible.  By looking at its chemical composition, specifically the THC:CBD ratio, the classification can be much more accurate and denote which strain may be dominant. The three types of classifications, type 1, type 2, and type 3, give more insight to the actual composition of the plant than by just comparing such physical features as leaf shape and plant height.

References:

  1. Cervantes, J. The Cannabis Encyclopedia: The Definitive Guide to Cultivation & Consumption of Medical Marijuana. Van Patten Publishing; 2015.
  2. Punja ZK, Rodriguez G, Chen S. Assessing genetic diversity in Cannabis sativa using molecular approaches. In Cannabis sativa L.-Botany and Biotechnology 2017 (pp. 395-418). Springer, Cham.
  3. ElSohly MA, Lata H, Chandra S. Cannabis Sativa L.–Botany and Biotechnology. Springer; 2017.
  4. Cisar J. Genomic and strain diversity. MCST608 Lecture Slides. University of Maryland School of Pharmacy.

Temperature effects on cannabis growth

Growing the cannabis plant is relatively easy and straightforward.  The plant is hardy to a wide range of temperatures.  Growing at an industrial scale, however, is much different, as temperature and humidity can affect the growth rate of the plant as well as flower quality.  For such a multibillion-dollar industry as cannabis, growth temperature is extremely important to help maintain high quality and consistency among the entire cannabis crop.

              The cannabis business is expected to grow exponentially as more states legalize both medicinal and recreational uses for the plant.  With revenue projected at around $20 billion dollars by 2022, growers have an incentive to maximize the quality and quantity of their product.1  While several factors, such as hours of sunlight and soil content, contribute to plant health, temperature plays an important role in growth rate and quality of flower production.  Throughout the four stages of growth, seedling, vegetation, flowering, and late flowering, the cannabis plant prefers certain temperatures to produce at the best levels.1 As well, depending on what the grower is trying to achieve, for instance THC content, temperature is also important.  The strain of cannabis also determines the optimum temperature for production.  There are strains that prefer high temperatures, such as Kaya Gold, because they are originally from warmer climates.1 It appears that African and Hawaiian strains also tend to be more heat resistant, while autoflowering strains originating in Siberia are often heat sensitive.1  While strain type does matter, in general, certain temperature ranges and drops during the night are appropriate for most plant types.

              The best range to grow cannabis is between 22 – 24o C during the day and 2 – 5oC during the night.  The cannabis plant, however, does not react well to changes is temperature of more than 8oC at a time.  More that this can shock the plant and severely affect growth rate.2 In the seedling stage, cannabis prefers temperatures in the 24 – 27oC.3  Clone cuttings also prefer the same temperature range.4 In the vegetation stage, when the plant produces its signature leaves, the best temperature range is 21 – 26oC.  Flowering plants seem to prefer a smaller range of temperatures, around 20 – 24oC.4 Finally, the late flowering period, which is when the plant reaches maturity over six to 12 weeks, temperature between 21 – 27oC seem to produce the best quality flower.3 Colder temperatures tend to affect cannabis much more negatively than warmer temperatures. In warmer temperatures, growth may slow, and flowers tend to be less dense, but the plant can still thrive.  On the other hand, when temperatures are too low, the root system is affected, and nutrient absorption is lowered. This can cause a deficiency in vital minerals such as magnesium.5 Mold and other contaminants also thrive at lower temperatures and may form on the root systems. As well, under 15oC the leaves will start to curl and the plant will eventually die.6  

              There are many factors that influence the cannabis plant during its cultivation.  Temperature is one of the most important of these that can contribute to growth rate and flower quality.  In general, cannabis prefers warmer temperatures because of the warmer climates from which they arise.  While temperature is strain dependent, as a whole, cannabis does not like large temperature swings and cannot survive below 15oC.  Too high temperatures can stunt growth and create sparse flowers.  Industrial scale growers regulate temperature very closely, as it can greatly affect the overall quality and quantity of their product.

References:

  1. Cannabis temperature tutorial. Grow weed easy website. https://www.growweedeasy.com/temperature#why-temperature-matters-to-YOU-as-a-grower. Accessed on June 15, 2020.
  2. Cannabis temperature for indoor grow rooms. Green CulturED website. https://www.greencultured.co/cannabis-temperature-indoor-grow-rooms. Accessed on June 15, 2020.
  3. Temperatures and medical cannabis growing from seedling to harvest. SensoScientific website. https://www.sensoscientific.com/blog-temperatures-and-medical-cannabis. Accessed on June 15, 2020.
  4. What’s the best grow room temperature and humidity level? High Times website. https://hightimes.com/grow/best-grow-room-temperature. Accessed on June 15, 2020.
  5. The effect of cold on cannabis plants. Alchimia website. https://www.alchimiaweb.com/blogen/the-cold-during-a-cannabis-plant-crop. Accessed on June 15, 2020.
  6. The ideal temperature for growing cannabis. Cannaconnection website. https://www.cannaconnection.com/blog/2245-ideal-temperature-growing. Accessed on June 15, 2020.