26 June 2015

THC-a Tincture for Paediatric Seizures

Knowledge Is Power When Fighting Illness

There Is An Effective, Non-CBD, Non-Psychoactive Way To Control Seizures With Cannabis

Most of us have heard about the wave of medical 'marijuana' refugees descending upon cannabis-friendly destinations like Colorado in the United States (US). Many were and are families who have children suffering from Dravet syndrome and other severe forms of intractable epilepsy and paediatric seizures. Ever since CNN correspondent Dr Sanjay Gupta’s documentary, 'Weed', more and more parents are willing for their children to try Cannabidiol (CBD) oil. Demand for the particulary high-CBD cannabis strain, Charlotte’s Web, has gone crazy since Dr Gupta’s show aired, because it was mentioned by name. What many parents don’t realise, upon first entering the initially bewildering world of medical cannabis, is that there are a number of other high-CBD strains as well, some with numbers higher than those of Charlotte’s Web.

Fifteen US state legislatures already have 'CBD-only' legislation, meaning they have legalised Cannabidiol (CBD) oil, whilst Tetrahydrocannabinol (THC), remains illegal. Other more conservative states such as Alabama were considering same. This is particularly unfortunate for a number of reasons: 
  1. research has shown that cannabinoids, including THC and CBD, work most effectively in combination with each other, through syngergistic effects; and, 
  2. the passage of 'CBD-only' legislation serves to increase and emphasise the 'scariness' and 'otherness' of THC. Demonising THC is just inane, as it is one of the best, most non-toxic anti-inflammatories, anti-tumour agents, antioxidants and neuroprotectants known.
And beyond that, almost none of these parents and other patients realise they could fight seizures just as effectively with THC which hasn’t been decarboxylated with heat. That is, Tetrahydrocannabinolic acid, THC acid or THC-a. Furthermore, THC-a is no more psychoactive than CBD, thus allaying parental concerns about getting their children 'high'. THC-a is one of the cannabinoids primarily found in fresh cannabis, although in variable amounts, according to CannLabs. Once the cannabis plant is exposed to heat, such as smoking or vaporising, THC-a decarboxylates to THC, the form that gives euphoric effects. What happens on a molecular level is that the carbon dioxide in the cannabis is released; as a carbon atom in the acid is lost, THC-a is converted to psycho-active THC.

THC-a, found in the flowers, leaves and stems of young cannabis plants, is biosynthesised by the trichomes. It plays a critical role in protecting the trichomes and thus the plants themselves from insects and other predators.

Screen Shot 2014-02-18 at 3.00.22 PM
The progression of cannabis from flower to extract

Although THC-a has no psychoactive effects of its own, it acts as a cannabinoid receptor agonist and in so doing provides neuroprotective (brain protection) effects. THC-a has also been shown to be an anti-inflammatory agent, has anti-proliferative qualities (help inhibit growth of cancerous cells), as well as anti-spasmodic effects, useful for epileptic patients. THC-a works just as well as CBD for seizure control, and is cheaper and more accessible than CBD (especially in the speculative environment created by CBD’s recently skyrocketing popularity).

In contrast to the specialised, low-THC/high CBD plants needed to make CBD extracts, any high-THC cannabis strain can be used to make THC-a tincture. Prominent Australian cannabis breeder/researcher Mark Heinrich told Toke Signals, “As it is THC-a, there is no issue of the 'high', so that makes strain choice less selective. Truly, this is globally available to even the poorest people”, Mark said. “I have sent this simple method to doctors in India, Pakistan, Bangladesh, China and more. This is HUGE, and it is so simple. There is no need to spend big money on CBD if THC-a is just as good. We are getting good results with CBD-a, CBD, THC-a, and CBN. Right now, the predators and the sharks are making a killing off CBD, but make no mistake, THC-a works just as well and we have proof. We want everyone to have access to the tutorials to empower them to be able to make their own and not be reliant on CBD merchants. What’s even better, the information is FREE, how cool is that, mate? And think how many folks can now get help - empowerment of parents”, Mark said.

Epsilon Apothecaries, founded in 2006 and based in Sacramento, California, has a downloadable Extraction Basics Guide (pdf), the Epsilon Essentials” Guide Series, comprising a novice approach to the creation of three special supplements: tincture extract of cannabis, essential extract of cannabis, and supplemental extract of cannabis. Readers can learn how to create therapeutic grade supplements at home, following in the footsteps of Epsilon’s decade-long track record of success in a variety of cases.

The Epsilon Essentials Guide is free of charge, the company’s website says, "All we ask is your respect in return".

Adapted from Parents THC-a Tincture Works Just As Well As CBD for Paediatric Seizures first published February 2014

23 June 2015

Treating Opioid Addiction/s with Cannabis

Most of today's illegal drugs originally had medicinal uses. Opiates are effective short-term pain killers but are not always effective for chronic pain and there are side effects and risks with long-term use of opioid pain relievers. Heroin, a very pure form of opiate, was developed by the Bayer company to treat wounded soldiers and send them back into battle as heroes (hence the name 'hero-in'). It was used medicinally in many countries for many years. Ecstasy (MDMA) was first synthesised in 1912 and later used in psychotherapy. Cocaine was advocated by Sigmund Freud as a cure for heroin addiction.

Research has shown that cannabis, while criminalised at the federal level in the US and illegal across Australia, can be effective as a substitute for treating opioid addicts and preventing overdoses. In the early 1900's in Australia, cannabis was not consumed on a large scale, although it was readily available for sale as cigarettes called 'Cigares de Joy' (until the 1920's). From the mid-19th century to the 1930's, American physicians prescribed cannabis for a plethora of indications and cannabis tinctures could be bought over the counter to treat a range of ailments. Before the 1960's, when the notion of 'recreational' drug use became a cultural phenomenon, most drug dependencies resulted from medicinal uses of drugs like heroin and morphine.

In 1970 US Congress classified cannabis as a Schedule I substance, illegal, and without medicinal value. In Australia, cannabis is currently a Schedule 9 'prohibited' substance. Simultaneous with prohibition, cannabis became the most widely used illicit recreational 'drug' in the US, a substance generally regarded as pleasurable and relaxing without the addictive dangers of opioids or stimulants. Meanwhile, cannabis never lost its cachet in alternative medicine circles, going mainstream in 1995 when California became the first state to legalise medicinal use, despite the federal ban. Little about cannabis is straightforward. Its main active ingredient, delta-9-Tetrahydrocannabinol (THC), was not isolated until 1964, and not until the 1990's were the far-reaching modulatory activities of the Endocannabinoid System (ECS) in the human body appreciated. This system's elucidation raises the possibility of many promising pharmaceutical applications.

Many, many studies support the therapeutic benefits of cannabinoids, (Google Scholar returns 20,400 results) including the psycho-active THC, to treat a wide range of conditions including nausea, weight loss, chronic pain, depression and a variety of mental health conditions and neurological diseases. The scientific debate over the harms and benefits of cannabis has impeded US federal lawmakers from moving forward on cannabis legislation reform. As a result, in 23 US states and Washington DC, medicinal cannabis has been legalised by popular vote. Australia is still waiting for a legitimate debate to begin, even though a recent AU$33.7m donation to Sydney University for cannabis research could be a starting point. 

Among drug treatment specialists, cannabis remains controversial. Although research has shown cannabis to be an alternative treatment for more serious drug addiction, addiction treatment specialists still view cannabis as highly addictive and dangerous. These views handicap policy reform, however, research shows cannabis could be a big part of the solution to the problem of opioid drug addiction in the US, Australia and worldwide. The World Health Organisation (WHO) estimates that worldwide, 69,000 people die from opioid overdose each year.

In an article in November 2014 an addict reported that telling people his story of recovery from addiction always proved controversial. However, it’s a story echoed by the experiences of countless others, usually airbrushed out of mainstream addiction narratives. He emerged from nearly 10 years of addiction to cocaine and heroin without sticking to a '12-Step' program and without becoming totally abstinent from all 'drugs' - in fact, using cannabis was a key part of his success. In the early days of recovery, using cannabis was a vital way to stave off his cravings for heroin, short-circuiting the urge and allowing quiet self-reflection instead. His fears would subside and he was able to regroup. Having used methadone for years, he found that using cannabis instead had an amazingly positive effect on him. His story seemed to resonate with many others. “Trying to maintain complete abstinence was like hanging onto the side of a cliff; it was just a matter of time until I got tired and let go”, commented one reader. The US National Epidemiological Survey on Alcohol and Related Conditions (NESARC) states that over 90% of people with substance use disorders overcome them without Alcoholics Anonymous (AA) or Narcotics Anonymous (NA, in both the US and Australia) or any formal treatment.

“There is a reason they call it ‘marijuana maintenance’ in AA”, said an addict who hadn’t used alcohol or other drugs in his 14 years in the program. “Many people get and stay off the hard 'shit' smoking 'pot'. In AA, where the goal is complete abstinence, that is a no-no … but as we all know, most junkie AA guys will, in candour, say, ‘You’re smoking weed? That’s not a drug!’ I mean, after every meeting I’ve ever been to, everybody rushes outside to light a cigarette and glug down a few cups of coffee. So it’s not surprising you’re getting some people looking at that and saying, ‘Hey, no fair. How come you can smoke tobacco and still be considered sober, but if I smoke marijuana it’s considered a relapse?’ After all, they’re both mood-altering substances but marijuana is the healthier of the two.”

“Certainly, I have clients who use it in this way,” says Dr Adi Jaffe when asked for his professional opinion on the pros and cons of using cannabis as a tool to wean off other drugs. Jaffe is a UCLA-trained addiction expert and a regular contributor to Psychology Today. He draws from his personal experiences with meth addiction when working with clients at his addiction treatment centre in Los Angeles. “When you think about it, this is classic harm reduction methodology, replacing a more harmful and dangerous drug with a lesser one to improve coping while reducing consequences. Harm reduction literature in general supports this idea as a positive step in recovery. If someone struggles with anxiety, they need something to help with it, whether that be neurofeedback, talk therapy or 'weed'”. Dr Jaffe notes, “My sense is that most typical 12-Step followers look at the practice unfavourably" and it’s certainly true that not everybody is happy with the idea of the erosion of cannabis’s forbidden status within the recovery community.

The once-taboo idea of using cannabis as a tool for people who want to stop using 'dangerous drugs' is catching on. In 2013, the Centre for Addictions Research of British Columbia, Canada published a study in the journal, Addiction Research & Theory, Cannabis as a substitute for alcohol and other drugs: A dispensary-based survey of substitution effect in Canadian medical cannabis patients. The results: Over 41% stated they used cannabis as a substitute for alcohol, 36.1% used cannabis as a substitute for illicit substances and 67.8% used cannabis as a substitute for prescription drugs. The three main reasons cited for cannabis-related substitution are 'less withdrawal' (67.7%), 'fewer side-effects' (60.4%) and 'better symptom management' suggesting that many patients may have already identified cannabis as an effective and potentially safer adjunct or alternative to their prescription drug regimen. 75.5% of respondents cited that they substituted cannabis for at least one other substance.

A study in the Journal of American Medicine reported that US states where medical 'marijuana' is legal had 25% fewer opioid overdoses. This tracks with other research indicating people use cannabis to stay off hard drugs. Could it be that instead of being a gateway to addiction, cannabis is a gateway to recovery? It’s a question that is likely to resonate as more states debate legalising cannabis in the midst of a crisis involving other drugs.

In Australia the National Opioid Pharmacotherapy Statistics Annual Data (NOPSAD) collection is a set of jurisdictional data that includes information about clients accessing pharmacotherapy for the treatment of opioid dependence among other things. Currently in Australia, opioid dependence may be treated by replacing the drug of dependence with one of the following longer-acting opioids:
  • methadone
  • buprenorphine
  • buprenorphine/naloxone.
These drugs are known as opioid pharmacotherapies. Over 48,000 Australians were on a course of pharmacotherapy treatment for their opioid dependence in June 2014.

Botanical cannabis (whole plant) attracts notoriety and controversy. Given the far-flung influence of endocannabinoids throughout the body, it is not surprising that botanical cannabis has traditionally been used to combat so many ills. In modern times, it has become an option of last resort for those for whom available pharmaceuticals have proven ineffective, including individuals with intractable nausea and vomiting, those dealing with cancer chemotherapy or anorexia in human immunodeficiency virus disease. This is the same substance, of course, that delights recreational users, blurring the boundary between health care and pleasure.

Cannabis is now legal for adult recreational use in Colorado, Washington state, Oregon, Alaska and Washington, DC. Like addiction, recovery is tightly bound by time and culture: If history had played out differently, with cannabis remaining legal and tobacco illegal (something that would almost certainly have saved millions of lives), cannabis might be seen as an acceptable part of recovery, while tobacco would clearly be a relapse. The same holds true for caffeine. High-dose caffeine, as anyone who has gotten jittery, talkative and paranoid from it can attest, is a serious stimulant and the fact that we don’t see it as a drug relates more to history than to science. Similarly, although cannabis can cause immediate impairment while tobacco does not, the serious long-term effects of tobacco use make it a good candidate for being named the single most powerfully addictive drug known.

Resources include;
Blurred Boundaries: The Therapeutics and Politics of Medical Marijuana
Cannabis The Exit Drug
Marijuana Use and Opiate Addiction
Can Medical-marijuana-curb-the-heroin-epidemic
Hot Topics-Drugs History

19 June 2015

Myth and Reality: Cannabis and Hemp

Cannabis Hemp Engraving
F P Nodder, May 1788
One of the most common misunderstandings about cannabis and hemp is that cannabis is the female and hemp is the male of the plant; in fact, nothing could be further from the truth. A simple botany lesson shows the botanical name of a plant consists of 'Botanical Latin' words, denoting a generic name (the genus) and the specific epithet (the species, usually two words, but can be three).

Cannabis sativa L., is a member of the Cannabaceae family. Cannabis is the plant genus, sativa (Latin for 'cultivated') is the species (and is included in many plant species names, e.g., rice is Oryza sativa L.), and the 'L.' (not always used) denotes the authority who first named the species, Carolus (Carl) Linnaeus, the Swiss botanist considered the 'Father of Taxonomy'.

Cannabis sativa L., is;
  • an annual,
  • herbaceous - denoting or relating to herbs (in the botanical sense),
  • usually dioecious - either exclusively male or exclusively female,
  • or monoecious - having the stamen (male, pollen-containing anther and filament) and the pistil (female, ovule-bearing) in the same plant (hermaphrodite).
Thus, as the Help End Marijuana Prohibition (HEMP) Party of Australia so rightly point out, cannabis is a herb.

A high-resin crop, cannabis is generally planted about 1.2-1.5m (four to five feet) apart and mostly used for its medicinal/therapeutic leaves and buds. Hemp is a low-resin crop, generally planted about 10 cm (four inches) apart, mostly used for its versatile stalk and seed. Different types of cannabis are classified as strains and different kinds of hemp are classified as varieties and cultivars.

Hemp was, for medieval Europeans, a generic term used to describe any fibre. With European expansion, fibre plants encountered during exploration were commonly called 'hemp'. Thus there is a bewildering variety of plants carrying the name hemp, including; Manila hemp (abacá, Musa textilis), Sisal hemp (Agave sisalana), New Zealand hemp/flax (Phormium tenax), Brown/Madras/Sunn hemp (Crotalaria juncea), Indian hemp (jute, Corchorus capsularis or C. clitorus) and Indian hemp (Apocynum cannabinum).

Cannabis Sativa Botanical Illustration
John Sowerby 1883
The botanical confusion was compounded by the introduction of one word, 'marihuana' (now commonly 'marijuana'). The word was first coined in the 1894 Scribner's Magazine feature "The American Congo" by John G. Bourke. Bourke was describing the native flora that flourished on the banks of the Rio Grande River that forms the border between the US state of Texas and Mexico. The term was adopted by the United States Bureau of Narcotics in the 1930's to describe all forms of Cannabis sativa L., and to this day, North Americans, in particular, continue to call the plant 'marijuana' without regard to botanical distinctions. 

The international definition of hemp was developed by a Canadian researcher, Ernest Small, in 1971. His arbitrary 0.3% THC limit became standard around the world as the official limit for 'legal' hemp, after he published a little-known, but very influential book, The Species Problem in Cannabis. In his book, Small discussed how “there is not any natural point at which the cannabinoid content can be used to distinguish strains of hemp and marijuana,” despite this he continued to “draw an arbitrary line on the continuum of cannabis types and decided that 0.3% THC in a sifted batch of cannabis flowers was the difference between hemp and marijuana” and this continues to add to the controversy and confusion as to what truly constitutes the difference between cannabis and hemp.

Hemp is an agricultural commodity that is cultivated for use in the production of a wide range of products including; foods and beverages, cosmetics, personal care products, nutritional supplements, fabrics and textiles, yarns and spun fibres, paper, construction and insulation materials, and other manufactured goods. Hemp can be grown as a fibre, seed, or other dual-purpose crop. In 2015, some estimate that the global market for hemp consists of more than 25,000 products.

Popular Mechanics dubbed hemp “the new billion dollar crop” in 1938, claiming that it “can be used to produce more than 25,000 products, ranging from dynamite to cellophane.” And when World War II demanded the full industrial might of the US, hemp restrictions were temporarily lifted and production reached its peak in 1943 when American farmers grew 150 million pounds of hemp. It was manufactured into shoes, ropes, fire hoses and even parachute webbing for soldiers fighting the war. After 1943, production plummeted and the anti-narcotic regime kicked back into effect.

Hemp seed oil is valued primarily for its nutritional properties as well as for the health benefits associated with it. Although its fatty acid composition is most often noted, with oil content ranging from 25-35%, whole hemp seed is additionally comprised of approximately 20-25% protein, 20-30% carbohydrates, and 10-15% fibre, along with trace minerals. A complete source of all essential amino and fatty acids, hemp seed oil is a complete nutritional source. In addition, constituents exist within the oil that have been shown to exhibit pharmacological activity.

In Australia, due to the current outdated and draconian laws (and ignorance on behalf of law enforcement in particular), it is illegal to consume hemp products unless you are an animal. Australians can, however, use hemp products topically. Food Standards Australia New Zealand (FSANZ) state on their website;

Hemp or industrial hemp is a Cannabis plant species (Cannabis sativa). Historically, hemp has been used as a source of fibre and oil. Cannabis extracts have also been used in medicine for a variety of ailments. Hemp is different to other varieties of Cannabis sativa, commonly referred to as marijuana. Hemp contains no, or very low levels of THC (delta 9-tetrahydrocannabinol), the chemical associated with the psychoactive properties of marijuana. Hemp is cultivated worldwide, including in Australia and New Zealand (under strict licensing arrangements) and is currently used in Australia as a source of clothing and building products. Hemp seeds contain protein, vitamins and minerals and polyunsaturated fatty acids, particularly omega-3 fatty acids. Hemp seed food products may provide an alternative dietary source of these nutrients. At present, hemp cannot be used in food in Australia and New Zealand as it is prohibited in the Australia New Zealand Food Standards Code. However, hemp oil has been permitted in NZ since 2002 under the New Zealand Food (Safety) Regulations. 
Hemp is used in other countries, including in Europe, Canada and the United States, in a range of foods including health bars, salad oils, non-soy tofu, non-dairy cheeses and as an additive to baked goods. It can also be used as the whole seed, raw or roasted.

But this was the answer to the question of re-legalising hemp for human consumption (January 2015);
Review of Low THC Hemp as a Food. Application 1039 – low tetrahydrocannabinol (THC) hemp as a food. The Forum in December 2012 requested FSANZ review its decision. FSANZ has reviewed its decision and re-affirmed its support of variation to the Code. The Forum noted FSANZ found foods derived from seeds of low THC hemp do not present any safety concerns as food and concerns regarding the impact on police THC drug testing fall beyond the remit of FSANZ. The Forum resolved to reject the proposed variation to Standard 1.4.4 (Prohibited and Restricted Plants and Fungi) resulting from Application A1039. Several concerns were raised by Forum Members, including law enforcement issues, particularly from a policing perspective in relation to roadside drug testing, cannabidiol levels as well as the marketing of hemp in food may send a confused message to consumers about the acceptability and safety of cannabis. The Forum agreed further work would be undertaken promptly to consider law enforcement, roadside drug testing and marketing concerns in consultation with relevant Ministers.
Law enforcement is the main reason hemp is not available legally as a food source in both Australia and New Zealand and we are the only two countries in the entire world where this idiocy is so.

Cannabis Sativa Botanical Illustration
The strict laws surrounding both cannabis and hemp have made research very difficult. Of the thousands of academic and research bodies in the US and Canada alone, whom would be equipped to perform agricultural or medical research on this unique species, only around 40 had actual research licenses to study the plant in a limited context. Despite these barriers, researchers have made progress in understanding the way cannabis works medicinally and therapeutically to assist in managing an ever-expanding list of disorders. What’s more, developments in hemp technology continue to reveal new and intriguing ways that this plant can contribute to society in the future. In 2014, researchers at the University of Alberta created a supercapacitor using raw hemp material, making the manufacturing of cheap, fast-charging batteries from hemp a real possibility. Hemp fibre is also being used to develop new forms of renewable plastic, which has made it a common material in the car parts industry. 

But as re-legalisation spreads across the globe, the opportunities to explore the potential of cannabis grows too. The possibilities are endless, and that is one thing cannabis and hemp have in common.

Resources include:

13 June 2015

Cannabis Baker: Decarbing and Olive Oil

Author Owen Smith from the Cannadian Cannabis Digest began his foray into the role of a medical cannabis caregiver at the bakery of the Victoria Cannabis Buyers Club (V-CBC) in 2008. Previous baking experience and a keen interest in learning about the cannabis plant as medicine made him an ideal candidate. He learned a great deal over the next year until he was arrested late 2009 but the response to his arrest was a constitutional trial that made cannabis extracts legal for patients in British Columbia (BC) in 2012.

Owen designed a video tutorial to explain the simple steps used to decarboxylate and extract the cannabinoids into vegetable oils to make a variety of products. This accompanies the dispensaries’ recipe book which only covers the basics of simple extraction, an art which has grown into a modern science in places where extract producers have been legally permitted to work. The recipes and methods continue to be revised and can be viewed at the V-CBC website.

Decarboxylation is the act of heating the plant material carefully to activate the THC-a (dormant acid form). This process happens naturally as the plant matter dries, but through a series of tests, we determined that heating at approximately 150°C (300°F) for 30 minutes can transform close to 98% of the inactive cannabinoids. Chemically, this process removes CO2 from the THC molecule, making it available to the cannabinoid receptors. The chart shows the results of decarboxylation over three tests with grapeseed oil. The left column measures how many milligrams of THC are found in a single ‘Ryanol’ capsule, while the bottom bar shows the temperatures used for the three testing sessions.

For the first test we used a double-boiler to cook the leaf into the grapeseed oil for 5-6 hours, which is the technique we had used for over 10 years. The second test involved heating the leaf for 30 minutes at 135°C (275°F) before double boiling the leaf. For the third test, we increased the temperature to 150°C (300°F) for 30 minutes before adding it to the oil. As the chart shows, the third and final test maximised the conversion of THC-a to active THC; increasing the temperature any more would risk combustion or breakdown of the cannabinoids. The decarboxylation process can be performed before the creation of any medicinal cannabis product to maximise the presence of active medicinal ingredients.

Decarboxylation transforms cannabinoid acids into their active states. Once this is performed you may immerse the dried cannabis into a medium of some sort to facilitate ingestion. Now the question arises, what medium should you use? At this stage you can decide to concentrate your medicine or dilute it. Diluting in vegetable oil may make it easier to measure a dose: two tablespoons is easier to measure than two 'grains of rice' and may deliver the same effect. In either case, at this point your dried cannabis will fuse with the carrier, shedding it’s medicinal compounds into the solution. (NB: In Canada, medicinal cannabis use was restricted to 'dried marihuana' only, forcing patients to keep all of the plant material in the solution, a highly impractical and arbitrary rule).

Capsule Guide from the V-CBC website
When making 'medibles' (medicated edibles) a measured amount of extracted medicine can be stirred into a recipe, providing consistent, long-lasting relief. Dispensaries like the V-CBC provide diluted extract products of varying strengths that are suited to their members needs. Monitoring your response to dosage takes time. The mantra ‘start low, go slow’ is advised when becoming familiar with edible products as some individuals require only a fraction of what others may need to ingest. 
Dutch researcher Arno Hazekamp conducted some of the initial research required to understand cannabis extraction into various mediums. "Recognising the need for more information on quality and safety issues regarding Cannabis oils, an analytical study was performed to compare several generally used preparation methods on the basis of content of cannabinoids, terpenes and residual solvent components. Solvents used include ethanol, naphtha, petroleum ether and olive oil".
IACM Journal 2006;1(1):1-4

Arno found olive oil was the most beneficial medium “based on the fact that it extracted higher amounts of terpenes than other solvents/methods, especially when using an extended heating time" (120 min; protocol 5, Figure 2, above). The oil needs to be heated up only to the boiling point of water (by placing a glass container with the product in a pan of boiling water) which prevents over-heating the oil. After cooling down and filtering the oil, e.g., by using a 'French' coffee press/coffee plunger (forbidden at the time by Health Canada), the product is immediately ready for consumption. As a trade-off, however, olive oil extract cannot be concentrated by evaporation, which means patients will need to consume a larger volume of it in order to get the same therapeutic effects.
Olive oil is cheap, non-toxic and doesn’t produce flammable gasses. It saturates the cells as it carries the cannabinoids across the skin or stomach lining. Cannabinoids are fat soluble so the additional oil increases their bioavailability. Extra virgin olive oil is preferable; stored away from light, air, and heat. There is hope that one day extracts will be produced on a commercial scale. For now, if you area making an edible or topical preparation at home, olive oil is probably the top choice.

01 June 2015

Cannabidiolic acid (CBD-a) and Cannabidiols (CBD's)

There are now around 111 known natural cannabinoids as reported in the scientific literature. In 2005, researchers from the University of Mississippi published a detailed review of the then 70 known cannabinoids. They have since isolated and described about 28 more cannabinoid derivatives, and a couple were reported by a group in Italy. In 2015, University of Mississippi scientists discovered seven new naturally occurring cannabinoids.

Cannabidiolic acid (CBD-a)
Until recently, CBD-a was thought to be a minor cannabinoid, only a small part of the overall cannabinoid profile. However, higher amounts have been seen in ruderalis strains and some recent hybrids have exhibited elevated levels of CBD-a, at potentially higher than THC-a. Just like THC-a, when heated, CBD-a decarboxylates; as THC-a becomes THC, so CBD-a becomes CBD. Like CBD, CBD-a is not psychoactive.

Cannabinoids, when heated (smoked, vaporised or baked into edibles) decarboxylate (decarboxylated forms might be produced biosynthetically and while drying, but acidic forms are the major product). Decarboxylation products are Δ9-THC, CBD and CBC. The 'first cannabinoid' also decarboxylates, from CBG-a to CBG.

CBD-a's therapeutic and medicinal values include:
Anti-emetic (reduces vomiting and nausea),
Anti-bacterial agent (slows growth of bacteria),
Anti-inflammatory (reduces inflammation systemically),
Anti-proliferative (inhibits cancer cell growth).

And while there hasn’t been much research done on CBD-a yet, the research that has been done is quite promising. Using the search term, Cannabidiolic acid, Google Scholar returns over 400 results for 2015 alone (1,420 since 2014 [over 10,000 all told]) and Science.gov (US federal government resource) returns 520 results (from over 16,000).
Cannabidiolic Acid (CBD-a)

CBD-a requires a temperature of 120°C (248°F) to decarboxylate and the LD50 (lethal dose) is 5,000 mg/kg (for rats) with a toxic concentration in humans (Inhalation TCLo, Toxic Concentration Low) of 15,000 mg/kg.

Cannabidiol (CBD)

The flowers and leaves of some 'industrial' hemp strains may be a viable source of CBD, but hemp is by no means an optimal source. Hemp typically contains far less CBD than CBD-rich cannabis. Huge amounts of industrial hemp are required to extract small amounts of CBD, raising the risk of toxic contaminants (hemp is a 'bio-accumulator'; drawing heavy metals from the soil). Single-molecule CBD synthesised in a lab or extracted and refined from industrial hemp lacks critical medicinal terpenes and secondary cannabinoids found in cannabis strains. These compounds interact with CBD and THC to enhance their therapeutic benefits.

CBD indirectly stimulates endogenous cannabinoid signalling by suppressing the enzyme 'fatty acid amide hydroxylase' (FAAH). This enzyme breaks down anandamide, a naturally occurring endogenous cannabinoid neurotransmitter, or 'endogenous ligand' which binds CB1 receptors which are concentrated in the brain and central nervous system. Because FAAH is responsible for breaking down anandamide, less FAAH means more anandamide (and greater CB1 activation) in the body for longer. By inhibiting the enzyme that metabolises and destroys anandamide, CBD enhances the body’s innate protective endocannabinoid response. At the same time, CBD powerfully opposes the action of THC at the CB1 receptor, thereby muting the psychoactive effects of THC. CBD also stimulates the release of 2-AG, another endocannabinoid that activates both CB1 and CB2 receptors. CB2 receptors are predominant in the peripheral nervous and immune systems.

Several studies have documented CBD’s role as a PPAR-gamma agonist (peroxisome proliferator activated receptors, PPAR's, a group of three nuclear receptors; PPAR-alpha, PPAR-gamma and PPAR-delta). Cannabidiol also promotes PPAR-alpha activity by inhibiting FAAH; the metabolic enzyme that breaks down several endogenous fatty acid compounds known as N-acylethanolamides. Two other N-acylethanolamides, N-palmitoylethanolamide (PEA) and N-oleoylethanolamide (OEA), bind directly to PPAR-alpha. By suppressing the FAAH enzyme and increasing PEA and OEA levels, cannabidiol indirectly activates PPAR-alpha. Higher levels of PEA and OEA result in enhanced PPAR-alpha transmission. Deficient PPAR-alpha signalling has been linked to schizophrenia.

Whereas CBD does not bind to either of the two known cannabinoid receptors, it has been shown to directly interact with other, so-called 'G-protein-coupled' receptors, to confer its medicinal effect. CBD binds to the TRPV-1 receptor which is known to mediate pain perception, inflammation and body temperature. TRPV or 'transient receptor potential cation channel subfamily V' is referred to by scientists as the 'vanilloid receptor' (named after the vanilla bean). Vanilla contains eugenol, an essential oil that has antiseptic and analgesic properties which also helps unclog blood vessels. Historically, the vanilla bean has been used as a folk cure for headaches. Capsaicin (a vanilloid), the pungent compound in hot chilli peppers, is a well known activator of the TRVP-1 receptor. CBD is a TRPV-1 'agonist' or stimulant and this seems to be one of the reasons why CBD-rich cannabis may be a particularly effective treatment for neuropathic pain.

There is also growing medical interest in the gene-regulating properties of CBD. In 2012, Israeli scientists identified more than 1,200 genes affected by CBD: 680 'gene transcripts' were up-regulated (turned on) and 524 were down-regulated (turned off) by CBD in a probe that focused on CBD’s role in zinc homoeostasis. “The results show that CBD ... affects the expression of genes involved in zinc homoeostasis and suggest that the regulation of zinc levels could have an important role through which CBD may exert its anti-oxidant and anti-inflammatory effects”, the Israeli research team concluded.

Studies indicate that CBD influences the expression of some genes by directly activating PPAR-gamma which has promising therapeutic implications, particularly with respect to cancer and metabolic disorders. PPAR's are triggered by hormones, endogenous fatty acids and various nutritional compounds. When activated, PPAR's bind to certain segments of DNA to promote or prevent transcription of specific genes. Many of the genes regulated by PPAR's are involved in energy homoeostasis, lipid uptake and metabolism, insulin sensitivity and other metabolic functions. Big Pharma recognises the importance of these nuclear receptors. Thus far, two classes of pharmaceutical PPAR activators - fibrates and thiazolidinediones - have been approved by the US Food and Drug Administration.

CBD is usually taken orally as a cannabis-based concentrate or extract. However, compared to smoking or vaporising, ingesting cannabinoids orally poses a number of drawbacks, including inconsistent absorption and a delayed effect. Vaporising is considered a healthier alternative to smoking and decarboxylation is reached at 160-180°C (320-356°F). However, when vaporised, CBD produces dense vapour that can be irritating to the throat for some and generate significant coughing, with the vapours produced visibly different to the less dense vapours produced by THC.

Scientific and clinical studies underscore CBD’s potential as a treatment for a wide range of conditionsCBD's therapeutic and medicinal values include:

Alzheimer’s Disease / Dementia / Memory Loss - CBD’s strong neuro-protective and anti-oxidative effects work together to counteract ageing in the brain, fighting off memory loss and dementia. In 2011, an Italian research team reported that PPAR-gamma activation degrades amyloid-beta plaque, a key molecule in the development of Alzheimer’s disease. Cardiovascular, autoimmune, neurological disorders, cancers and the ageing process itself are all thought to have free radicals as a causative agent. Further, they are implicated in the formation of protein amyloid plaques - plaques that can attack neural synapses and prevent normal chemical and electrical signalling. By binding up these free radicals, antioxidants can minimise the plaque formation cycle associated with the progression of Alzheimer’s disease. 
Analgesic - relieves pain, including chronic and neuropathic.

Anti-bacterial agent - slows growth of bacteria.

♋ Anti-inflammatory - reduces inflammation systemically. "CBD affects the expression of genes involved in zinc homoeostasis and suggest that the regulation of zinc levels could have an important role through which CBD may exert its anti-oxidant and anti-inflammatory effects,” an Israeli research team concluded. Nutritional factors also influence PPAR signalling. At the 2013 International Cannabinoid Research Society Conference, Wageningen University (Netherlands) reported that the omega-3 fatty acid derivative docosahexaenoyl ethanolamine (DHEA) acts as an inhibitor of the COX-2 enzyme. So does CBD; this is one of the major reasons why CBD has potent anti-inflammatory properties. COX-2 is an enzyme that creates prostaglandins, a class of inflammatory compounds. Aspirin and all the other non-steroidal anti-inflammatory drugs are COX inhibitors.

♋ Anti-oxidant – prevents the damage of oxidation to other molecules in the body. The antioxidant properties of CBD exceed the antioxidant potency of either Vitamin C or E. CBD has been shown to be a potent anti-oxidant that mitigates the negative effects of oxygen free radicals. When combined with THC, the anti-oxidant properties of CBD grow even stronger. Once again, whole-plant cannabis therapeutics have been shown to be far greater than the sum of the herb’s individual medicinal components.

Angiogenesis (development of new blood vessels). According to a 2008 report by the University of Rome, both PPAR-alpha and PPAR-gamma agonists regulate angiogenesis, the creation of new blood vessels, particularly capillaries. In cancerous tumours, dysregulated angiogenesis leads to new blood vessels which provide tumours with nutrients, helping them to grow and metastasise. By directly activating PPAR-gamma and indirectly promoting PPAR-alpha activity, CBD may inhibit tumour angiogenesis. Three major complications associated with Diabetes Mellitus - retinopathy, neuropathy and nephropathy are all worsened by aberrant angiogenesis. Although numerous PPAR agonists have shown efficacy in preventing retinal angiogenesis, some studies report that activating PPAR's can amplify angiogenesis. But the overall scientific consensus seems to be that PPAR-alpha and PPAR-gamma agonists prevent angiogenesis.

♋ Anti-diabetic – CBD is the only cannabinoid identified that helps lower blood sugar levels. 

♋ Anti-emetic – reduces vomiting and nausea.

Anti-epileptic – reduces seizures and convulsions. In October 2013, the US FDA approved two clinical trials assessing the therapeutic uses of CBD in treating intractable epilepsy in children (Dravet Syndrome). The CBD preparations were made by British pharmaceutical company GW Pharmaceuticals. Dravet is a rare seizure disorder wherein children usually suffer their first intractable seizure before their first birthday and in exceptional cases seizures can last over 24 hours. In Australia, whole, organic cannabis extracts for intractable forms of epilepsy have been formulated from high-CBD cannabis strains that also include THC ('Entourage Effect').

♋ Anti-insomnia – aids with sleep.

♋ Anti-ischemic – CBD is the only cannabinoid identified that reduces the risk of artery blockage.

♋ Anti-proliferative - inhibits the growth of tumours / cancer cells. A study published in 2007 showed that CBD inhibited a particular gene, Id-1, which is responsible for the growth of cancer cells in the body. By inhibiting this gene CBD shuts down the growth of cancer cells, potentially stopping or even reversing tumour growth. Researchers at the California Pacific Medical Center have shown that CBD reduces brain cancer and breast cancer cell proliferation and metastasis by inhibiting the expression of the Id-1 gene. GPR55a G protein-coupled receptor that some researchers postulate may actually be a third cannabinoid receptor type (CB-3?), when activated, promotes cancer cell proliferation, according to a 2010 study by researchers at the Chinese Academy of Sciences. CBD is a GPR55 antagonist, as University of Aberdeen discovered, also in 2010. By blocking GPR55 signalling, CBD might act to decrease both bone re-absorption and cancer cell proliferation. This is one of many molecular pathways through which CBD exerts an anti-cancer effect. Best results were obtained when CBD was administered in combination with THC. ID-1 expression is implicated in several kinds of aggressive cancer.

Anti-psioratic – CBD is the only cannabinoid identified to treat psoriasis.

♋ Anti-psychotic – tranquilising effects relieve symptoms of psychosis; two terpenoids, Linalool and Myrcene, also help. CBD is a powerful anti-psychotic currently being considered for use in treating schizophrenia and other psychoses. CBD appears to have a very similar chemical profile to certain atypical anti-psychotic drugs. PPAR-alpha agonists in particular are indicated as an adjunct treatment for schizophrenia. Polymorphisms or mutations in the gene encoding PPAR-alpha are associated with schizophrenia. Furthermore, PPAR-alpha activation is both anti-inflammatory and can decrease dopamine release, thereby minimising schizophrenic symptoms. This may help to explain how and why CBD has anti-psychotic effects.

♋ Anti-spasmodic – suppresses muscle spasms.

♋ Anxiolytic (anti-anxiety) / Anti-depressant – CBD is the only cannabinoid identified that relieves anxiety, but two terpenoids also help (Linalool and Limonene). CBD may exert its anti-anxiety effect by activating adenosine receptors. Adenosine receptors play significant roles in cardiovascular function, regulating myocardial oxygen consumption and coronary blood flow. The adenosine (A2A) receptor has broad anti-inflammatory effects throughout the body. Adenosine receptors also play a significant role in the brain as they down-regulate release of other neurotransmitters (dopamine and glutamate). CBD also stimulates the 5-HT1a (hydroxytryptamine) receptor in the brain involved in the re-uptake of serotonin and other processes that aid depression and anxiety. The anti-depressant properties of CBD are very similar to the trycyclic anti-depressant Imipramine (also being evaluated for panic disorder). At the University of San Paulo in Brazil and King’s College in London, pioneering research into CBD and the neural correlates of anxiety have been studied. At high concentrations, CBD directly activates the 5-HT1A serotonin receptor, thereby conferring an anti-depressant effect. This receptor is implicated in a range of biological and neurological processes, including, but not necessarily limited to, anxiety, addiction, appetite, sleep, pain perception, nausea and vomiting. 5-HT receptors are activated by the neurotransmitter serotonin, found in both the central and peripheral nervous systems. 5-HT receptors trigger various intracellular cascades of chemical messages to produce either an excitatory or inhibitory response, depending on the chemical context of the message. CBD triggers an inhibitory response that slows down 5-HT1A signalling. In comparison, LSD, mescaline, magic mushrooms and several other hallucinogenic drugs activate a different type of 5-HT receptor that produces an excitatory response.

♋ Bone Stimulant – promotes bone growth. Some studies indicate that CBD may function as an antagonist that blocks, or deactivates, GPR55 which is widely expressed in the brain, especially in the cerebellum. It is involved in modulating blood pressure and bone density. GPR55 promotes osteoclast cell function, which facilitates bone re-absorption; over-active GPR55 receptor signalling is associated with osteoporosis.

♋ Immunosuppressive – CBD is the only cannabinoid identified that reduces function in the immune system.

Inflammatory Bowel Disease (Syndrome) / Crohn’s Disease - CBD shows a lot of promise for controlling the inflammatory responses and discomfort caused by Crohn’s disease and IBD/IBS. CBD has so much potential to regulate these diseases that it is being considered for a new class of IBD drugs.

♋ Intestinal Anti-prokinetic – CBD is the only cannabinoid identified that reduces small intestine contractions.

Neuroprotective – slows damage to the nervous system and brain.

Obesity and Metabolic Syndrome - most genes regulated by PPAR's (peroxisome proliferator activated receptors) are involved with lipid metabolism and energy storage. PPAR activation typically promotes glycolysis (glucose breakdown), lipolysis (lipid breakdown) and insulin sensitivity. These properties make PPAR activation a promising treatment for Type II Diabetes and obesity. The PPAR-activating drugs, fibrates and thiazolidinediones (PPAR-alpha agonists and PPAR-gamma agonists, respectively) have been approved to treat dyslipidemia (obesity) and insulin insensitivity in Type II Diabetics by the US FDA.

♋ Vasorelaxant – CBD is the only cannabinoid identified that reduces vascular tension.

List of Conditions treatable with Cannabidiol (Project CBD)

A search for 'Cannabidiol' in the US National Library of Medicine National Institutes of Health website, 'PubMed', returns 1,341 resultsIf you need more examples of research into CBD, check out Cannabis Research A-Z and/or CBD Research and Studies from 'Medical Jane'.

This is Part 2 of a four-part series on a lot of what is currently known about cannabinoids and covers one of the three major branches; Cannabidiols (CBD's) including Cannabidiolic acid (CBD-a). Part 1 covered CBG-a, The Precursor, and CBG. Part 3 will cover another of the three major branches of cannabinoids; Cannabichromenes (CBC's), including Cannabichromenic acid (CBC-a).

Reference sources included;

Study:New Cannabinoids Discovered
Safety Data Sheet-CBDa
A Chemotaxonomic Analysis of Cannabinoid Variation in Cannabis (Cannabaceae)
How Cbd Works Within Cells
Cannabinoid Profile CBDa
Cannabinoid Profile - CBD
How CBD Works

Cannabinoid Profile CBG
Granny Storm Crows List 2015