In just a few years, cannabidiol (CBD) has become immensely popular around the world. First of all, concentrated extracts allow the consumption of a large dose of . hemp is allowed only with the intent to produce fibers or seeds. . Additionally, as many as 26/46 samples (57%) had a THC content > 1%. In , the first cannabinoid receptor was identified (CB1) (Howlett et al ) and . Cannabidiol, a non-euphoriant phytocannabinoid common in certain strains, shares While THC has no activity at vanilloid receptors, CBD, like AEA, is a TRPV1 Initial experiences with medicinal extracts of cannabis for chronic pain. In a clinical trial THC did not have any significant effect on ongoing and . A mixture of mg THC and mg cannabidiol (CBD) lowered spasm .. Cohen C., Perrault G., Voltz C., Steinberg R., Soubrie P. SR, a central cannabinoid (CB(1)) .. Initial experiences with medicinal extracts of cannabis for chronic pain.
had CBD r/cannabis - with (cannabidiol) Has experiences any strains with high extracts, or CB anyone
Pregnant and breastfeeding women should probably avoid cannabis. Although research is limited and often contradictory, there is evidence linking cannabis to ectopic pregnancies, miscarriages, attention deficit disorders, and slightly below-average birth weights.
One final issue to mention, particularly affecting long-term cannabis users, is cannabinoid hyperemesis syndrome. This is a rare condition characterized by uncontrollable nausea, vomiting, and abdominal cramps, as well as a compulsion to take hot baths for relief.
It can usually be treated with abstinence. The threshold dose for high potency cannabis, smoked, is 0. A common dose is between 0. For medium potency cannabis, the common dose is 0. The effects from smoking are typically felt within the first 10 minutes—usually within the first minute—peaking at minutes before sloping off over the next hours. For oral consumption, the dosage is measured by THC content. More experienced users often take up to 20 mg or more at a time.
With the exception of sublingual tinctures, which have a similarly rapid onset to smoking,  the effects from orally consumed cannabis are felt within minutes, peaking at two to three hours and lasting for up to eight. Common effects include mood enhancement and euphoria, accompanied by laughter and relaxation, as well as an increased enjoyment of music, food, tactile sensations, and activities you normally find dull.
Thoughts tend to be more free flowing, often leading to creative and philosophical or spiritual insights. At higher doses, the flow of ideas can even become overwhelming. Panic attacks, confusion, memory loss, and depersonalization or derealization are some of the more negative effects of cannabis, along with the suppression of dreams.
Otherwise, visual effects tend to be limited to color enhancement, moderate closed-eye patterns, and increased sensitivity to light. Lethargic, slow movements are especially common on cannabis, even with the elevated heart rate. There are subtle differences between weed and hash as well, with the latter tending to give a clearer, more cerebral high. With edibles, there may be some anxiety and paranoia at first before giving way to a psychedelic body high and deep sleep.
Driving on cannabis, and especially on edibles and extracts, is strongly discouraged. While many find it makes them drive slower, it also slows down reactions, posing a danger on the road. Higher potency cannabis should be avoided in public anyway, at least the first time, as the effects can be overwhelming.
The presence of different strains and unevenly distributed THC in edibles can also make them hard to predict.
This involves starting with a L ow dose, E stablishing potency, going S low being patient for the onset of effects , and S upplementing as needed with more.
New cannabis smokers are often told to hold smoke in their lungs for as long as they can to fully absorb the cannabinoids. This is because early researchers measured THC by gas chromatography, which involved heating and therefore breaking down the molecule. The sample size is also much, much larger than it used to be. In the s, researchers were lucky if they had access to 18 seizures in a year, whereas nowadays they have access to thousands.
Evidence suggests that people only smoke as much as they need to reach their desired state. In other words, the higher the potency, the less users need—and ultimately, the fewer carcinogens they inhale. This Reefer Madness -style argument for continued prohibition has zero basis in fact. While it is true that most habitual drug users are exposed to cannabis before any harder drugs, this is only to be expected considering that cannabis is the most prevalent illicit substance worldwide.
But if it did, alcohol and tobacco would be the original gateway drugs, since most cocaine and heroin addicts are exposed to them even earlier. Withdrawal symptoms include irritability, lethargy, physical discomfort, difficulty sleeping, diminished appetite, and a loss of pleasure in once enjoyable activities anhedonia. Unlike withdrawal symptoms from other drugs, such as alcohol, tobacco, and heroin, these effects tend to be mild. They also tend to fade after two to four days, or within six weeks for heavy users.
The medical applications of cannabis are many and well known, and the list is continually growing. Substantial evidence, drawn from years of clinical research, supports its use as a treatment for nausea and vomiting in chemotherapy patients; appetite loss and wasting syndrome cachexia in HIV and cancer patients; spasticity in multiple sclerosis MS patients; and neuropathic or chronic pain, such as fibromyalgia.
In addition to the clinical evidence, numerous anecdotal reports link total remission to the regular use of cannabis oil.
Rick Simpson, for example, claims to have cured his skin cancer by applying high-THC cannabis oil directly to the affected area. Cannabis and synthetic cannabinoid-based medications may also be used to treat cancer-related symptoms.
For instance, Marinol works to stimulate appetite and reduce nausea and vomiting in chemotherapy patients, even when other antiemetics have failed. Studies have also found cannabis to be an effective analgesic, and one far safer than opioids. This is promising not only for cancer patients, but for sufferers of rheumatoid or osteoarthritis, as well as chronic pain in general.
Cannabis may also play an important role in stabilizing mood more generally. Not only do cannabinoids have an anti-depressant effect on serotonin release,  but chronic stress appears to downregulate endocannabinoid production. THC in particular may help treat depression by reducing negative bias in emotional processing.
A number of other studies, however, have associated cannabis with a higher incidence of depression or a deadening of emotion in general. Crucially for recovering addicts, it can also treat underlying issues like anxiety, depression, and trauma. According to one, it took just seven weeks for cannabis oil to improve the memory, mood, and physical mobility of a formerly catatonic patient.
When she was returned to a state-run facility and standard pharmaceutical treatment program, her condition again deteriorated. As an anti-inflammatory, for example, THC reduces inflammation in the brain and ultimately minimizes damage.
CBD has proven to be an effective treatment for epilepsy, including rare forms such as Lennox-Gastaut and Dravet syndromes—both of which afflict young children with frequent, devastating seizures. Among migraine sufferers, daily cannabis inhalation is shown to reduce the frequency of headaches from just over 10 migraines per month to fewer than five for Cannabinoids have also been found to significantly reduce the intraocular pressure, pupil restriction, and conjunctival hyperemia associated with glaucoma.
Unfortunately, the high doses required may not be suitable for elderly patients, due to the cardiovascular and psychoactive effects. Some other promising indications for cannabis include osteoporosis, diabetes, inflammatory skin diseases like eczema , allergic reactions, and organ transplant rejection.
This suggests that microdosing cannabis in later life could be a good defence against memory loss. Many people report enhanced creativity from cannabis—an effect that is supported by science. The psychospiritual benefits of cannabis include deeper meditation and a sense of oneness or unity with people, the planet, and the universe. For an up-to-date list, see here. Unfortunately, decriminalization does nothing to undermine the criminal supply chain.
In the Netherlands, where cannabis has long been decriminalized for sale in coffee shops, the coffee shops themselves are forced to rely on the unregulated black market to source their product. This raises ethical and economic concerns, as well as health issues, since many unregulated growers are thought to make heavy use of inorganic pesticides.
In the UK, against the recommendations of scientific advisors, medical professionals, politicians, and even police commissioners,   cannabis remains a Class B drug. Possession is punishable by up to five years in prison, an unlimited fine, or both. While MS patients and only MS patients are allowed to use Sativex, the drug is prohibitively expensive everywhere but Wales. In Canada, where cannabis is a Schedule II drug, possession has been punishable by up to six months in jail and a CAD fine for the first offense, and up to one year in jail and a CAD fine for subsequent offenses.
In addition to being able to buy cannabis from licensed producers or indeed sell it as one , Canadian adults will also be allowed to grow their own cannabis at home, as long as they have no more than 30 seeds in their possession and no more than four cannabis plants per residence. The use of organic solvents to make concentrated cannabis products e. In Australia, cannabis is legal for medical use and scientific research. Cannabis has also been decriminalized or partially decriminalized in a number of European countries, including Austria, Germany, Italy, and Portugal.
Cannabis stays in the blood and urine for days. In formerly chronic, daily users, it may be possible to detect cannabis for up to 90 days, but isolated occasional use tends to clear the system in less than 10—and sometimes as little as two. Some strains of cannabis, and especially edibles and extracts, can be overwhelmingly strong for beginners. This usually depends on set and setting. The impact of cannabis on forming long-term memories is more nuanced, appearing only to affect the spatial episodic memory.
This means you may be liable to forget locations and layouts more easily than you forget events. Although a lethal overdose is practically unheard of, cannabis does carry a number of potential risks. These include psychological dependence, legal repercussions, and, as with exercise, cardiovascular abnormalities. Try to relax yourself with deep breathing if you can, and make sure you stay hydrated.
Drink some orange juice to raise your blood sugar and lessen the high. A cold shower might also help, along with distractions like funny movies or calming music. CBD—which is effectively an antidote for THC—can also be taken as a tincture for rapid relief capsules take longer to work. Check here for state-by-state laws on cannabis cultivation in the US.
In the UK, for example, police may not even bother investigating unless more than nine plants are suspected. As of October in Canada, for example, when recreational use becomes legal, cultivation will be limited to a maximum of four plants per residence—unless of course you have a license.
Joints and blunts are popular for their simplicity, convenience, and rapid onset of effects—and there are plenty of variations to discover. On the other hand, they waste a lot of smoke and may be tricky to roll. Pipes are even more convenient, but a single hit can sometimes be insufficient for more experienced users. Bongs address this problem but often at the expense of portability, since they tend to be pretty large.
They also take some getting used to, so beginners may waste smoke or experience chest pain. Vaporizers are by far the most efficient method, offering a cleaner, healthier feel. Many vaporizers are also designed for discretion, such as models resembling regular asthma inhalers. On the other hand, they also take longer to kick in and can be far more potent when they do.
While cannabis marijuana, pot, etc. In compliance with regulations, hemp also has negligible amounts of THC and is therefore non-psychoactive. Hash is made by separating out the resinous trichomes from the rest of cannabis plant—either by sieve, hand, ice-water, or butane—and compressing them into a block or paste. Inferior quality hash may also contain adulterants for bulk, such as sand, henna, or plastic.
Since hash is a concentrated form of cannabis, it tends to have more THC than weed the whole dried buds. A joint is a hand-rolled cannabis cigarette containing around half a gram of cannabis. A blunt, on the other hand, is made by emptying the tobacco from a cigar and filling the shell with cannabis.
Pre-rolled blunt wraps can also be used for the purpose. Detailed instructions can be found here. On average, one gram of cannabis is likely to contain mg THC. However, this varies widely so it helps to know your strain. More information on calculating doses is available here.
Microdoses range between mg THC, but 5 mg is often suggested as a good starting point. Microdosing cannabis may help to relieve anxiety, depression, chronic pain, stress, inflammation, indigestion, and symptoms of ADHD.
For more information, read our guide. Different strains of cannabis have different effects — indica can be more sedative, while sativa can be more energizing. For more information about the different strains of cannabis, read here. Frequent cannabis use produces tolerance by decreasing the availability of CB1 receptors in the brain. But these should start to replenish after a couple of days of abstinence, returning to normal levels within four weeks. Cannabis is often taken alongside other drugs.
For example, combined with classical psychedelics like LSD or psilocybin, it tends to intensify and prolong the effects. Cannabis can also potentiate dissociatives like ketamine.
Combined with alcohol, though, it may lead to nausea and dizziness—especially when the alcohol comes first. Always remember that combining drugs—even with cannabis—can be risky.
For more information, click here. Founders of Western civilisation were prehistoric dope dealers. University of California Press. The Secret History of Cannabis in Japan. The Asia-Pacific Journal, 12 History of Cannabis as a Medicine. Plants of the Gods: Their Sacred, Healing, and Hallucinogenic Powers. History of cannabis as a medicine: Revista Brasileira de Psiquiatria, 28 2. A Collection of Bhang Recipes. The Encyclopedia of Psychoactive Plants: Ethnopharmacology and Its Applications.
It brings out the real you. Rastafari — Way of Life. The Secret History of the Marijuana Religion. The Chrism in the Gospel of Philip. Marijuana and the Bible.
A History of Marijuana. Queen Victoria on cannabis, and all the other things you never knew about drugs. Drugs and the Making of the Modern World. History of Cannabis in India. The Truth About Indicas and Sativas. Cannabis, a complex plant: Therapeutic Advances in Psychopharmacology, 2 6: British Journal of Pharmacology, Suppl 1: The Science of Marijuana.
The origins of Skunk. The Truth About Marijuana. One study reported that tolerance to some of the effects of cannabis, including tolerance to the "high", developed both when THC was administered orally 30 mg; q. There was no diminution of the appetite-stimulating effect from either route of administration. A clinical study that evaluated the effects of smoked cannabis on psychomotor function, working memory, risk-taking, subjective and physiological effects in occasional and frequent cannabis smokers following a controlled smoking regimen reported that when compared to frequent smokers, occasional smokers showed significantly more psychomotor impairment, more significant impairment of spatial working memory, significantly increased risk-taking and impulsivity, significantly higher scores for "high" ratings, for "stimulated" ratings, and more anxiety Reference Compared with frequent smokers, occasional smokers had significantly increased heart rates relative to baseline and higher systolic and diastolic blood pressure just after dosing.
These findings suggest that frequent cannabis users can develop some tolerance to some psychomotor impairments despite higher blood concentrations of THC. Occasional smokers also reported significantly longer and more intense subjective effects compared with frequent smokers who had higher THC concentrations suggesting tolerance can develop to the subjective effects. A clinical study evaluated the development of tolerance to the effects of around-the-clock oral administration of THC 20 mg every 3.
The morning THC dose increased intoxication ratings on day 2 but had less effects on days 4 after administration of a cumulative mg dose of THC and 6, while THC lowered blood pressure and increased heart rate over the six-day period suggesting the development of tolerance to the subjective intoxicating effects of THC and the absence of tolerance to its cardiovascular effects.
Tolerance to the subjective intoxicating effects of THC administered orally was manifested after a total exposure of mg of THC over the course of four days Reference Another clinical study reported that while heavy chronic cannabis smokers demonstrated tolerance to some of the behaviourally-impairing effects of THC, these subjects did not exhibit cross-tolerance to the impairing effects of alcohol, and alcohol potentiated the impairing effects of THC on measures such as divided attention Reference An uncontrolled, open-label extension study of an initial five-week randomized trial of nabiximols in patients with MS and central neuropathic pain reported the absence of pharmacological tolerance measured by a change in the mean daily dosage of nabiximols to cannabinoid-induced analgesia, even after an almost two-year treatment period in a group of select patients Reference Another long-term, open-label extension study of nabiximols in patients with spasticity caused by MS echoed these findings, also reporting the absence of pharmacological tolerance to the anti-spastic effects measured by a change in the mean daily dosage of nabiximols after almost one year of treatment Reference A multi-centre, prospective, cohort, long-term safety study of patients using cannabis as part of their pain management regimen for chronic non-cancer pain reported small and non-significant increases in daily dose over a one-year study period Reference More recently, a double-blind, placebo-controlled, three-way cross-over clinical study with regular cannabis users suggested that tolerance may not develop towards some of the acute effects on neurocognitive functions despite regular cannabis use Reference One hundred and twenty-two subjects who regularly used cannabis average duration of use: Acute administration of vapourized cannabis impaired performance across a wide range of neurocognitive domains: Frequency of cannabis use correlated significantly with change in subjective intoxication following cannabis administration and also correlated and interacted with changes in psychomotor performance meaning that subjective intoxication and psychomotor impairment following cannabis exposure decreased with increasing frequency of use, however the baseline for subjective intoxication and psychomotor impairment was already higher for frequent users compared to less frequent users likely owing to already elevated THC body burden which can cause sufficient levels of intoxication and mild psychomotor impairment.
The authors suggest that the neurocognitive functions of daily or near daily cannabis users can be substantially impaired from repeated cannabis use, during and beyond the initial phase of intoxication. Pharmacokinetic tolerance including changes in absorption, distribution, biotransformation and excretion has also been documented to occur with repeated cannabinoid administration, but apparently occurs to a lesser degree than pharmacodynamic tolerance Reference Dependence can be divided into two independent, but in certain situations interrelated concepts: The ECS has been implicated in the acquisition and maintenance of drug taking behaviour, and in various physiological and behavioural processes associated with psychological dependence or addiction Reference 2.
In the former DSM-IV diagnostic and statistical manual of mental disorders fourth edition , the term 'dependence' was closely related to the concept of addiction which may or may not include physical dependence, and is characterized by use despite harm, and loss of control over use Reference There is evidence that cannabis dependence physical and psychological occurs, especially with chronic, heavy use Reference Reference Reference In the new DSM-5, the term "cannabis dependence" has been replaced with the concept of a "cannabis use disorder" CUD which can range in intensity from mild to moderate to severe with severity based on the number of symptom criteria endorsed Reference For a list of symptoms, please refer to the DSM-5 Reference Risk factors for transition from use to dependence have been identified and include being young, male, poor, having a low level of educational attainment, urban residence, early substance use onset, use of another psychoactive substance, and co-occurrence of a psychiatric disorder Reference Notably, the transition to cannabis dependence occurs considerably more quickly than the transition to nicotine or alcohol dependence Reference These increases in both month and lifetime prevalence are thought to be driven by increases in the prevalence of cannabis users.
Higher frequency of cannabis use was associated with greater risk of disorder incidence and prevalence, supporting a dose-response association between cannabis use and risk of substance use disorders. Another study using the U. Survey respondents with month CUD differed significantly from others on all disability components of the survey, with disability increasing significantly, as cannabis disorder severity increased.
Comparing data between the NESARC - Wave 1 and - Wave 2 , one study reported that the prevalence of cannabis use more than doubled between the two waves of the survey Reference Furthermore, there was a large increase in CUD during this intervening time, with nearly 3 out of 10 cannabis users reporting a CUD in - A retrospective study among a nationally representative sample of 6 Australian adults examining the initiation of cannabis use and transition to CUD found that the mean time from first use to the onset of CUD was 3.
Younger age of initiation and other substance use were strong predictors of the transition from use to CUD. Social phobia and panic disorder were also associated with transition from cannabis use to CUD.
Male cannabis users had greater risk of CUD than female users, but among women, those with depression were more likely to develop a CUD. Early-onset of alcohol and daily cigarette smoking were each associated with marked increased risk of early initiation of cannabis use. A handful of clinical studies have examined the differences between men and women with respect to development of dependence, withdrawal symptoms and relapse Reference Physical dependence is most often manifested in the appearance of withdrawal symptoms when use is abruptly halted or discontinued.
Withdrawal symptoms associated with cessation of cannabis use oral or smoked appear within the first one to two days following discontinuation; peak effects typically occur between days 2 and 6 and most symptoms resolve within one to two weeks Reference - Reference Other symptoms appear to include depressed mood, chills, stomach pain, shakiness and sweating Reference Reference Reference Reference Cannabis withdrawal symptoms appear to be moderately inheritable with both genetic and environmental factors at play Reference There are also emerging reports of increased physical dependence with highly potent cannabis extracts e.
There are no approved pharmacotherapies for managing cannabis withdrawal symptoms Reference A range of medications have been explored including antidepressants e. Zolpidem has also been explored as a potential pharmacotherapy to specifically target abstinence-induced disruptions in sleep Reference Reference However, agonist substitution therapy e.
Self-titrated doses were lower and showed limited efficacy compared to high fixed doses and subjects typically reported significantly lower ratings of "high" and shorter duration of "high" with nabiximols and placebo compared to smoking cannabis.
A randomized, double-blind, placebo-controlled, six-day, inpatient clinical study of nabiximols as an agonist replacement therapy for cannabis withdrawal symptoms reported that nabiximols treatment attenuated cannabis withdrawal symptoms and improved patient retention in treatment Reference However, placebo was as effective as nabiximols in promoting long-term reductions in cannabis use at follow-up.
Nabiximols treatment significantly reduced the overall severity of cannabis withdrawal symptoms relative to placebo including effects on irritability, depression and craving as well as a more limited effect on sleep disturbance, anxiety, appetite loss, physical symptoms and restlessness.
A placebo-controlled, within-subject, clinical study demonstrated that nabilone 6 - 8 mg daily decreased cannabis withdrawal symptoms including abstinence-related irritability and disruptions in sleep and food intake in daily, non-treatment seeking cannabis smokers Reference It also decreased cannabis self-administration during abstinence in a laboratory model of relapse.
While nabilone did not engender subjective ratings associated with abuse liability i. A follow-up study found that nabilone 3 mg, b. A double-blind, placebo-controlled, week clinical trial testing lofexidine and dronabinol for the treatment of CUD reported no significant beneficial effect compared to placebo for promoting abstinence, reducing withdrawal symptoms, or retaining individuals in treatment Reference in contrast to a previous study that showed efficacy of 40 mg dronabinol daily vs.
A recent systematic review of the evidence of CBD as an intervention for addictive behaviours reported that to date, only 14 studies have been conducted, the majority in animals with only a handful in humans Reference The limited number of pre-clinical studies carried out to date suggest that CBD may have therapeutic potential for the treatment of opioid, cocaine and psychostimulant addiction, and some preliminary data suggest CBD may also be beneficial in cannabis and tobacco addiction in humans Reference The limited number of pre-clinical studies published thus far suggest CBD may have an impact on the intoxication and relapse phase of opioid addiction, while CBD does not appear to have an impact on the rewarding effects of stimulants e.
With respect to cannabis dependence, pre-clinical studies show that CBD is not reinforcing on its own, but its impact on cannabis-related dependence behaviour remains unclear Reference In one clinical study, a 19 year-old female with cannabis dependence exhibiting cannabis withdrawal symptoms upon cannabis cessation was administered up to mg of CBD range: In another human study, cannabis with a higher CBD to THC ratio was associated with lower ratings of pleasantness for drug stimuli explicit "liking" , but no group difference in "craving" or "stoned" ratings was noted Reference Reference However, a multi-site, double-blind, placebo-controlled study demonstrated that CBD - mg had no effect on subjective ratings associated with cannabis abuse liability Reference A randomized, double-blind, crossover clinical study in 10 healthy volunteers examining the effects of CBD on the intoxication phase of alcohol addiction reported no differences in feelings of "drunk", "drugged", or "bad" between the alcohol only and the alcohol and CBD groups Reference Reference No pre-clinical studies exist on the use of CBD for hallucinogen-, sedative-, tobacco-, or alcohol-addictive behaviours and no human studies exist on the use of CBD for opioid-, psychostimulant-, hallucinogen-, or sedative-addictive behaviours Reference The ECS is present in early development, is critical for neurodevelopment and maintains expression in the brain throughout life Reference Furthermore, the ECS undergoes dynamic changes during adolescence with significant fluctuations in both the levels and locations of the CB 1 receptor in the brain as well as changes in the levels of the endocannabinoids 2-AG and anandamide Reference The dynamic changes occurring in the ECS during adolescence also overlap with a significant period of neuronal plasticity that includes neuronal proliferation, rewiring and synaptogenesis, and dendritic pruning and myelination that occurs at the same time Reference This period of significant neuroplasticity does not appear to be complete until at least the age of 25 Reference Thus, this neurodevelopmental time window is critical for ensuring proper neurobehavioural and cognitive development and is also influenced by external stimuli, both positive and negative e.
Based on the available scientific evidence, youths are more susceptible to the adverse effects associated with cannabis use, especially chronic use Reference Reference Studies examining non-medical use of cannabis strongly suggest early onset i.
Based on the current available evidence, it is unclear for how long some or all of the neurocognitive effects persist following cessation of use. Some investigators have found certain cognitive deficits to persist for up to one year or longer after cannabis cessation, while others have demonstrated a far shorter period of recovery i. Though the data from human studies do not establish causality solely from cannabis use, the pre-clinical studies in animals do indicate that adolescent exposure to cannabinoids can catalyze molecular processes leading to functional deficits in adulthood - deficits that are not found following adult exposure to cannabis.
The authors note that definitive conclusions cannot be made yet as to whether cannabis use - on its own - negatively impacts the adolescent brain, and future research can help elucidate this relationship by integrating assessments of molecular, structural, and behavioral outcomes Reference Factors that may influence persistence of cognitive deficits can include age at onset of use, frequency and duration of use, co-morbidities, and use of other drugs tobacco, alcohol, and other psychoactive drugs.
While adverse effects associated with THC-predominant cannabis use in youth have been well documented, far less is known about the adverse effects associated with CBD-predominant cannabis use. Nevertheless, as mentioned above, the ECS plays important roles in nervous system development in utero as well as during youth see Section 7.
There is evidence to suggest that like the changes seen with the ECS during development and adolescence, there are changes in the ECS associated with ageing. In addition, the coupling of CB 1 receptors to G proteins is also reduced in specific brain areas in older animals Reference Age-related changes in the expression of components of the ECS appear similar in rodents and humans Reference Disruption of CB receptors appears to enhance age-related decline of a number of tissues suggesting an important role for the ECS in the control of the ageing process Reference In general, the elderly may be more sensitive to the effects of drugs acting on the CNS Reference A number of physiological factors may lie at the root of this increased sensitivity such as: There is very little information available on the effects of cannabis and cannabinoids in geriatric populations and based on current levels of evidence, no firm conclusions can be made with regard to the safety or efficacy of cannabinoid-based drugs in elderly patients but see below for one of the few clinical studies of safety carried out specifically in geriatric populations Reference Reference Reference Furthermore, as cannabinoids are lipophilic, they may tend to accumulate to a greater extent in elderly individuals since such individuals are more likely to have an increase in adipose tissue, a decrease in lean body mass and total body water, and an increase in the volume of distribution of lipophilic drugs Reference Lastly, age-related changes in hepatic function such as a decrease in hepatic blood flow and slower hepatic metabolism can slow the elimination of lipophilic drugs and increase the likelihood of adverse effects Reference A randomized, double-blind, placebo-controlled, cross-over clinical trial that evaluated the pharmacokinetics of THC in 10 older patients with dementia mean age 77 years over a week period reported that the median time to reach maximal concentration in the blood T max was between 1 and 2 h with THC pharmacokinetics increasing linearly with increasing dose but with wide inter-individual variation Reference Only one clinical study has thus far been carried out looking specifically at the safety of THC in an elderly population.
In this study, 12 adults aged 65 and older who were deemed to be healthy were included, and exclusion criteria included high falls risk, regular cannabis use, history of sensitivity to cannabis, drug and alcohol abuse, compromised cardiopulmonary function, and psychiatric comorbidities.
The most commonly reported health problems were hypertension and hypercholesterolemia and subjects reported using an average of 2 medications e. Adverse events first occurred within 20 min of dosing, with all adverse events occurring between 55 and min after dosing and resolving completely within 3. No moderate or serious adverse events were reported in this trial.
While this clinical study adds important information regarding the safety and tolerability of THC in a healthy elderly population, additional studies are needed to evaluate the safety and tolerability of cannabis and cannabinoids in elderly populations having various co-morbidities. In humans, sex-dependent differences have been often observed in the biological and behavioural effects of substances of abuse, including cannabis Reference In male animals, higher densities of CB 1 receptors have been observed in almost all cerebral regions analyzed whereas in females a more efficient coupling of the CB 1 receptor to downstream G-protein signaling has been observed Reference In humans, sex differences in CB 1 receptor density have also been reported, with men having higher receptor density compared to women Reference Sex-dependent differences have also been noted with respect to cannabinoid metabolism.
Pre-clinical studies in females report increased metabolism of THC to hydroxy-THC compared to males where THC was also biotransformed to at least three different, less active metabolites Reference There is also evidence to suggest that effects of cannabinoids vary as a function of fluctuations in reproductive hormones Reference Reference Together, these findings suggest that the neurobiological mechanism underlying the sex-dependent effects of cannabinoids may arise from sexual dimorphism in the ECS and THC metabolism, but also from the effects of fluctuations in hormone levels on the ECS Reference Reference There is also evidence to suggest sex-dependent differences in subjective effects and development of dependence, withdrawal symptoms, relapse and incidence of mood disorders.
Data combined from four double-blind, within-subject studies measuring the effects of smoked "active" cannabis 3. These findings suggest that, at least among near-daily cannabis users, women may be more sensitive to the subjective effects of cannabis, especially effects related to cannabis abuse liability compared to men.
Another study demonstrated dose-dependent sex differences in subjective responses to orally administered THC Reference In this study, women showed greater subjective effects at the lowest dose 5 mg , whereas men showed greater subjective responses at the highest 15 mg dose. Together, these studies suggest that while women may be more sensitive to the subjective effects of THC at lower doses, they may develop tolerance to these effects at higher doses, which could, for example, have implications for the development of dependence.
For example, while cannabis use among men is more prevalent and men appear to be more likely than women to become dependent on cannabis, women tend to have shorter intervals between the onset of use and regular use or development of dependence commonly referred to as the "telescoping effect" Reference In addition, women abstaining from cannabis use reported more withdrawal symptoms, with some being more severe, than those seen in men and which have been linked to relapse Reference Reference Women with CUD also present with higher rates of certain comorbid health problems such as mood and anxiety disorders Reference Reference Reference The College of Family Physicians of Canada, along with other provincial medical regulatory colleges, has issued a guidance document in for authorizing the use of cannabis for medical purposes.
Please consult these and any other official guidance documents, as applicable, for additional information regarding dosing and other matters associated with authorizing cannabis for medical purposes. Cannabis has many variables that do not fit well with the typical medical model for drug prescribing Reference While precise dosages have not been established, some "rough" dosing guidelines for smoked or vapourized cannabis have been published see below.
Besides smoking and vapourization, cannabis is known to be consumed in baked goods such as cookies or brownies, or drunk as teas or infusions. However, absorption of these products by the oral route is slow and erratic, varies with the ingested matrix e.
Other forms of preparation reported in the lay literature include cannabis-based butters, candies, edibles, oils, compresses, creams, ointments, and tinctures Reference 80 Reference - Reference but again, limited dosing information exists here with much of the information being anecdotal in nature.
Dosing remains highly individualized and relies largely on titration Reference Patients with no prior experience with cannabis and initiating cannabis therapy for the first time are cautioned to begin at the very lowest dose and to stop therapy if unacceptable or undesirable side effects occur. Subsequent dose escalation should be done slowly, once experience with the subjective effects is fully appreciated, to effect or tolerability. If intolerable adverse effects appear without significant benefit, dosing should be tapered and stopped.
Tapering guidelines have not been published, but the existence of a withdrawal syndrome see Section 2. Clinical studies of cannabis and cannabis-based products for therapeutic purposes are limited to studies carried out with dried cannabis that was smoked or vapourized and with synthetic or natural cannabis-based products that have received market authorization i. As such, providing precise dosing guidelines for such products is not possible although existing sources of information can be used as a reference point see below.
Naturally, dosing will vary according to the underlying disorder and the many other variables mentioned above. Average daily dose of dronabinol is 20 mg and maximal recommended daily dose is 40 mg Reference Doses less than 1 mg of THC per dosing session may further avoid incidence and risks of adverse effects. Various surveys published in the peer-reviewed literature have suggested that the majority of people using smoked or orally ingested cannabis for medical purposes reported using between 10 and 20 g of cannabis per week or approximately 1 to 3 g of cannabis per day Reference Reference Reference An international, web-based, cross-sectional survey examining patients' experiences with different methods of cannabis intake reported that from among a group of self-selected participants, from 31 countries, the vast majority preferred inhalation over other means of administration e.
Mean daily doses with smoked or vapourized cannabis were 3. Information regarding cannabinoid potencies of cannabis products i. Daily frequency of use for smoking was six times per day, whereas with vapourizing it was five times per day.
First onset of effects for smoking were noted on average around 7 min after start of smoking, 6. Other data suggests that those patients who use cannabis for medical purposes use up to one gram or less per day. For example, data from the Netherlands suggests the average daily dose of dried cannabis for medical purposes stood at 0. Canadian market data collected from licensed producers under the Access to Cannabis for Medical Purposes Regulations ACMPRs showed that, from April to March , clients had been authorized by their healthcare practitioners to use, monthly, an average of 2.
However, since this data is collected per licensed producer, it does not include cases where clients split their authorization into two or more authorizations in order to register with more than one licensed producer at a time or personal production registrations with Health Canada Reference To fulfill orders for oils, licensed producers equate oil to dried cannabis based on the formulation of their oil products.
On average, licensed producers equate 1 g of dried cannabis to 6. Using this average conversion factor, healthcare practitioners have authorized an equivalent average of Satisfaction ratings for criteria such as onset of effects and ease of dose finding were reported to be higher for smoking and vapourizing i.
However, prescription cannabinoid medications e. Satisfaction ratings in terms of side-effects were higher for non-prescription unregulated cannabis products, with the inhaled route rated best, although the survey did not ask specific questions about the types of side effects. Satisfaction ratings were only slightly higher for orally ingested cannabis products for criteria such as duration of effects.
The majority of survey participants had indicated having used cannabis products prior to onset of their medical condition. A prospective, open-label, longitudinal study of patients with treatment resistant chronic pain reported that patients titrate their cannabis dose starting with one puff or one drop of cannabis oil per day, increasing in increments of one puff or one drop of oil per dose, three times per day until satisfactory pain relief was achieved or side effects appeared Reference Mean monthly prescribed amount of cannabis was 43 g or 1.
Data from randomized, double-blind, placebo-controlled clinical studies of smoked or vapourized cannabis used a daily dose of up to 3.
In contrast to the gram amounts of cannabis used with smoked, vapourized, and oral routes of administration, the mean daily amounts for prescription cannabinoids such as dronabinol were 30 mg, for nabilone 4.
With respect to the relationship between dosing and psychotropic effects , it has been estimated that an inhaled dose of 0. Furthermore, it has been estimated that between one and three puffs of higher potency cannabis would be sufficient to produce significant psychoactive effects Reference One study has shown that while cannabis smokers titrate their dose of THC by inhaling lower volumes of smoke when smoking "strong" joints i.
For oral administration, a dose of 0. Other provincial bodies may also provide guidelines on monitoring Reference The College of Family Physicians of Canada has recently published a simplified guideline for prescribing medical cannabinoids in primary care Reference The recommendations are as follows:.
The majority of clinical trials with smoked cannabis for medical purposes have used joints of dried cannabis weighing between and mg. Estimates that are more recent suggest the mean weight of cannabis in a joint is mg Reference In addition, expectation of drug reward can also influence smoking dynamics Reference Little reliable information exists regarding conversion of a "smoked dose" of THC to an equivalent oral dose.
It is also important to emphasize that this "conversion factor" appears to relate mostly to psychoactive effects e. Further rigorous comparative pharmacology studies are required. In addition, no comparative studies have been done with vaping. In addition, this theoretical conversion factor may or may not apply for therapeutic effects. Indeed, it is important to highlight that two studies reported that individuals using cannabis for therapeutic purposes indicated they used approximately similar gram amounts of cannabis regardless of route of administration Reference Reference A single-dose, open-label, clinical trial of patients with neuropathic pain and using very low doses of inhaled THC reported a statistically significant improvement in neuropathic pain with minimal adverse effects Reference THC administration was associated with a statistically significant reduction in baseline VAS for pain intensity of 3.
These above-mentioned studies suggest that, at least in the case of chronic neuropathic pain, psychoactive effects can be separated from therapeutic effects and that very low doses of THC may actually be sufficient to produce analgesia while keeping psychoactive effects to a minimum. A review of U. Product has been discontinued by the manufacturer post-market; as of February ; not for safety reasons. Newfoundland and Labrador; NS: Prince Edward Island; QC: The pharmacokinetic information described in Section 2.
Tea prepared from Cannabis flowering tops and leaves has been documented, but no data are available regarding efficacy Reference On the other hand, to reduce or prevent CINV, a dosage of 5 mg t.
In either case, the dose should be carefully titrated to avoid the manifestation of adverse effects. The second dose is usually administered 1 to 3 h before chemotherapy. If required, the administration of nabilone can be continued up to 24 h after the chemotherapeutic agent is given.
The maximum recommended daily dose is 6 mg in divided doses. Dose adjustment titration may be required in order to attain the desired response, or to improve tolerability. More recent clinical trials report starting doses of nabilone of 0. Data from an open-label longitudinal study of cannabis oil for patients with treatment-resistant chronic non-cancer pain reported that patients titrated their cannabis oil dose starting with one drop of cannabis oil per day, increasing in increments of one drop of oil per dose, three times per day, until satisfactory analgesia was achieved or until side effects appeared Reference Maximum daily dose was 5 mg b.
On subsequent days, the number of sprays can be increased by one spray per day, as needed and tolerated.
A fifteen-minute time gap should be allowed between sprays. During the initial titration, sprays should be evenly spread out over the day. If at any time unacceptable adverse reactions such as dizziness or other CNS-type reactions develop, dosing should be suspended or reduced or the dosing schedule changed to increase the time intervals between doses. According to the drug product monograph, the average dose of nabiximols is five sprays per day i.
The majority of patients appear to require 12 sprays or less; dosage should be adjusted as needed and tolerated. Administration of four sprays to healthy volunteers total The Dutch Office of Medicinal Cannabis has published "rough" guidelines on the use of vapourizers Reference Although the amount of cannabis used per day needs to be determined on an individual basis, the initial dosage should be low and may be increased slowly as symptoms indicate.
The amount of cannabis to be placed in the vapourizer may vary depending on the type of vapourizer used. The levels of cannabinoids released into the vapour phase increased with the temperature of vapourization Reference Participants inhaled as much of the mg dose of dried cannabis 3.
In another study, patients followed a similar "cued-puff" procedure and inhaled 4 puffs, followed by an additional round of between 4 and 8 puffs 2 h later for a total of between 8 and 12 puffs over a 2 h period Reference Subjects inhaled 4 puffs at the beginning of the testing session, followed by an additional round of between 4 and 8 puffs 3 h later for a total of between 8 and 12 puffs over a 3 h period.
While there are countless anecdotal reports concerning the therapeutic uses of cannabis, clinical studies supporting the safety and efficacy of cannabis for therapeutic purposes in a variety of disorders are limited, but slowly increasing in number. Furthermore, the current level of evidence for the safety and efficacy of cannabis for medical purposes does not meet the requirements of the Food and Drugs Act and its Regulations except for those products that have received a notice of compliance and market authorization from Health Canada.
It has been repeatedly noted that the psychotropic side effects associated with the use of psychoactive cannabinoids have been found to limit their therapeutic utility Reference 23 Reference 55 Reference 57 Reference Reference A comprehensive review of 72 controlled clinical studies evaluating the therapeutic effects of cannabinoids mainly orally administered THC, nabilone, nabiximols, or an oral extract of cannabis up to the year reported that cannabinoids present an interesting therapeutic potential as anti-emetics, appetite stimulants in debilitating diseases cancer and AIDS , analgesics, and in the treatment of MS, SCIs, Tourette's syndrome TS , epilepsy, and glaucoma Reference However, a more recent systematic review and meta-analysis of randomized clinical trials of cannabinoids i.
Compared with placebo, cannabinoids were associated with a greater average number of patients showing a complete improvement in nausea and vomiting, reduction in pain, a greater average reduction in numerical rating scale pain assessment, and average reduction in the Ashworth spasticity scale Reference An incredibly detailed and authoritative article on CBD.
Looking forward to reading more articles for CBD Week. CBD Week is a great idea and I hope you explore other topics in a similar fashion. No Hoosier should have to leave their home, their family, their friends to obtain a life changing medication. Try to stick with taking a dose, then waiting to be genuinely mindful of the effect before taking more — this will prevent you from raising your tolerance and will allow you to figure out what the right dose for you is.
For example, homemade edibles often have an uneven distribution, due to the handmade nature of home baking. Some dispensaries even in states where cannabis is only medically legal mostly are aimed at recreational users. At medical places, employees will be knowledgeable about dosages, the menu will be very clear about dosages and usages, there will be a wide range of CBD products, and some will even offer additional medical or educational services such as workshops or visits with cannabis-friendly herbalists.
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She was unable to keep up with her twin sister. She was catatonic and nothing the doctors could do for her helped. Some of them almost killing her. After exhausting all other treatments, her we turned to the internet to see what alternative treatments may be available.
So we made the decision to give cannabis oil to Charlotte and from the first dose we noticed results. Jaqie Angel Warrior is my two-year old who has suffered from multiple types of seizures since she was five months old. Dozens of medications, including Depakote and klonopin, failed to control the thousands of seizures and caused terrible side effects. Most children need some significant quantity of THC to see transformational results.
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Cannabinoids in health and disease
Dietary supplements containing varying amounts of CBD have been touted as Adams and Alexander R. Todd—Mechoulam's interest was piqued by anecdotal stock, labs, and they were extracting cannabidiol and other cannabis . High- CBD strains of cannabis and other CBD-based products are. CBD oil is made by extracting CBD from the cannabis plant, then Studies have shown that CBD may help reduce chronic pain by and THC in people with cancer-related pain who did not experience High blood pressure is linked to higher risks of a number of health Are There Any Side Effects?. But what evidence do we have regarding cannabis and its effects on sleep? Currently research on the medicinal use of cannabis is restricted due to the legal THC can cause anxiety reactions but higher concentrations of cannabidiol may Certainly anyone who has used alcohol to help sleep knows that in the long run.