TLC Alpha-CAT CBD:THC ratio First and last line on this plate demonstrate a CBD:THC ratio. While the both in the middle are more around a CBD:THC. What do CBD to THC ratios mean and what can they really do? A variety of vape oils, tinctures, salves, and edibles with numbers like , , , , 2: 1, and ), while Pure Ratios cut down to three (, , and ). The optimal dose involves the right ratio of CBD to THC in the right quantity for Preclinical studies have shown that full-spectrum CBD-rich cannabis oil (with a.
In THC 8) What Oil? an CBD and Ratio
Anandamide is principally, but not exclusively, produced by the transfer of arachidonic acid from phosphatidylcholine to phosphatidylethanolamine by N-acyltransferase to yield N-arachidonoylphosphatidylethanolamine NAPE. While anandamide and 2-AG are both derivatives of arachidonic acid, they are synthesized by pathways distinct from those used to synthesize eicosanoids Reference Nevertheless, it appears that there may be a certain amount of cross talk between the eicosanoid and endocannabinoid pathways Reference The receptors are encoded by separate genes located on separate chromosomes; in humans, the CB 1 receptor gene CNR1 locus is found on chromosome 5q15 whereas the CB 2 receptor gene CNR2 locus is located on chromosome 1p36 Reference The CNR1 coding sequence consists of one exon encoding a protein of amino acids Reference As with the CNR1 coding sequence, the CNR2 coding sequence consists of only one exon, but it encodes a shorter protein amino acids in length Reference Anandamide is a partial agonist at cannabinoid receptors, and binds with slightly higher affinity at CB 1 compared to CB 2 receptors Reference 2 Reference In the central nervous system CNS , the overall effect of CB 1 receptor activation is suppression of neurotransmitter release 5-hydroxytryptamine 5-HT , glutamate, acetylcholine, GABA, noradrenaline, dopamine, D-aspartate, cholecystokinin at both excitatory and inhibitory synapses with both short and long-term effects Reference 2 Reference 18 Reference Inhibition of neurotransmitter release occurs through a retrograde signaling mechanism whereby endocannabinoids synthesized and released from the cell membrane of post-synaptic neurons diffuse backwards across the synaptic cleft and bind to CB 1 receptors located on the pre-synaptic terminals Figure 1 Reference 3.
This retrograde signaling mechanism permits the regulation of neurotransmission in a precise spatio-temporal manner Reference 3. The CB 1 receptor is one of the most abundant G-protein coupled receptors in the central and peripheral nervous systems Reference It has been detected in the cerebral cortex, hippocampus, amygdala, basal ganglia, substantia nigra pars reticulata, internal and external segments of the globus pallidus and cerebellum molecular layer , and at central and peripheral levels of the pain pathways including the periaqueductal gray matter, the rostral ventrolateral medulla, the dorsal primary afferent spinal cord regions including peripheral nociceptors, and spinal interneurons Reference 4 Reference 23 Reference CB 1 receptor density is highest in the cingulate gyrus, the frontal cortex, the hippocampus, the cerebellum, and the basal ganglia Reference 5.
Relatively little CB 1 receptor expression is found in the thalamus and the primary motor cortex Reference 5. The CB 1 receptor is also expressed in many other organs and tissues including adipocytes, leukocytes, spleen, heart, lung, the gastrointestinal GI tract liver, pancreas, stomach, and the small and large intestine , kidney, bladder, reproductive organs, skeletal muscle, bone, joints, and skin Reference 25 - Reference CB 2 receptors are most highly concentrated in the tissues and cells of the immune system such as the leukocytes and the spleen, but can also be found in bone and to a lesser degree in liver and in nerve cells including astrocytes, oligodendrocytes and microglia, and even some neuronal sub-populations Reference 44 Reference Besides the well-known CB 1 and CB 2 receptors, a number of different cannabinoids are believed to bind to a number of other molecular targets.
For additional details on this subject please see Section 2. Modulation of these other cannabinoid targets adds additional layers of complexity to the known myriad effects of cannabinoids. Endocannabinoid signaling is rapidly terminated by the action of two hydrolytic enzymes: Signal termination is important in ensuring that biological activities are properly regulated and prolonged signaling activity, such as by the use of cannabis, can have potentially deleterious effects Reference 52 Reference Dysregulation of the ECS appears to be connected to a number of pathological conditions, with the changes in the functioning of the system being either protective or harmful Reference However, a major and consistent therapeutic challenge confronting the routine use of THC-predominant cannabis and psychoactive cannabinoids e.
THC in the clinic has remained that of achieving selective targeting of the site of disease or symptoms and the sparing of other bodily regions such as the mood and cognitive centres of the brain Reference 23 Reference 54 - Reference The CB 1 receptor is highly expressed in the developing brain Reference For example, CB 1 receptors are highly expressed from early fetal stages, beginning as early as E Furthermore, in the adult brain, the CB 1 receptor appears to be localized on the axonal plasma membrane and in somatodendritic endosomes, whereas in fetal brain the CB 1 receptor is mostly localized to endosomes both in axons and in the somatodendritic region Reference The available evidence suggests a neurodevelopmental role for the ECS including in functions such as survival, proliferation, migration and differentiation of neuronal progenitors Reference CB 1 receptor activation, in response to stimulation by endocannabinoids, such as 2-AG and anandamide, promotes these functions but delays the transition from multipotent, proliferating, and migration-competent progenitor phenotype towards a more settled, well-differentiated, post-mitotic neuronal phenotype Reference 60 Reference In vitro studies examining the effects of CB 1 receptor activation in primary neuronal cultures suggest that the CB 1 receptor is mainly a negative regulator of neurite growth since activation of the receptor results in growth cone arrest, repulsion or collapse and thereby influences the ability of axons to reach their targets Reference However, these CB 1 receptor-mediated responses may be surmountable by the effects of local growth-promoting effectors at the growth cone and the balance between the effects of endocannabinoids and growth factors would determine the overall outcome of neuronal development.
The CB 1 receptor appears also to act as a negative regulator of synaptogenesis and in doing so can also affect the fate of neuronal communication Reference Exposure to cannabinoids that activate the CB 1 receptor such as THC during developmental periods of nervous system development such as during embryonic development in pregnancy could alter the course of normal neuronal development in offspring and negatively affect normal brain function potentially causing long-lasting impairment of a number of cognitive functions and behaviours Reference 61 and also see Sections 2.
For example, a study conducted in pregnant mice using a low dose of THC has been shown to alter the expression level of 35 proteins in the fetal cerebrum Reference Furthermore this study concretely identified a specific molecular target for THC in the developing CNS whose modifications can directly and permanently impair the wiring of neuronal networks during corticogenesis by enabling formation of ectopic neuronal filopodia and altering axonal morphology Reference Another in vitro study with retinal ganglion cell explants showed that CBD decreased neuronal growth cone size and filopodia number as well as total projection length and induced growth cone collapse and neurite retraction i.
See text for additional details. Figure adapted from Reference 64 - Reference The leaves and flowering tops of Cannabis contain over distinct compounds distributed among 18 different chemical classes, and harbor over different phytocannabinoids Reference 68 - Reference 71 The principal phytocannabinoids appear to be deltatetrahydrocannabinol i.
In the living plant, these phytocannabinoids exist as both inactive monocarboxylic acids e. Furthermore, pyrolysis such as by smoking transforms each of the hundreds of compounds in cannabis into a number of other compounds, many of which remain to be characterized both chemically and pharmacologically.
Therefore, cannabis can be considered a very crude drug containing a very large number of chemical and pharmacological constituents, the properties of which are only slowly being understood. However, Canadian licensed producers of cannabis for medical purposes have now made available a large variety of cannabis strains containing varying levels of THC and CBD, including THC-predominant, CBD-predominant or balanced strains for patients who have received authorization from their healthcare practitioner to access cannabis for medical purposes.
For more information, please consult the Health Canada authorized licensed producers of cannabis for medical purposes website. The large number of compounds found in cannabis spans many chemical classes including phytocannabinoids, nitrogenous compounds, amino acids, proteins, enzymes, glycoproteins, hydrocarbons, simple alcohols, aldehydes, ketones and acids, fatty acids, simple esters and lactones, steroids, terpenes, non-cannabinoid phenols, flavonoids, vitamins, and pigments Reference Furthermore, differences in the presence and the relative abundance of some of these various components have been investigated, and differences in various components have been noted between cannabis extract, vapour, and smoke, and also between cannabis varieties Reference Of note, cannabis smoke contains many compounds not observed in either extracts or vapour, including a number which are known or suspected carcinogens or mutagens Reference 81 - Reference Moreover, comparisons between cannabis smoke and tobacco smoke have shown that the former contains many of the same carcinogenic chemicals found in the latter Reference 82 Reference 84 see Section 7.
Relatively little is known about the pharmacological actions of the various other compounds found within cannabis e. However, it is believed that some of these compounds e. Terpenes vary widely among cannabis varieties and are thought to be primarily responsible for differences in fragrance among the different Cannabis strains Reference Furthermore, it is thought that terpenes may contribute to the distinctive smoking qualities and possibly to the character of the "high" associated with smoking cannabis Reference 75 , but again, this has not been studied in any detail.
The concept that terpenes may somehow modify or enhance the physiological effects of the cannabinoids Reference 85 Reference 86 ,i. As the temperature increases, the rate of decarboxylation increases: Heat, light, humidity, acidity and oxidation all affect the stability of cannabis and phytocannabinoids Reference 91 Reference Sevigny has provided the following formula for calculating decay of THC: For specific stability and storage conditions for cannabis provided by licensed commercial producers in Canada, please consult information provided by the licensed commercial producers.
Its effects are not well studied but it appears to have some possible immunosuppressive properties in a small number of in vitro studies Reference Cannabigerolic acid has a similar profile.
CBD lacks detectable psychoactivity and does not appear to bind to either CB 1 or CB 2 receptors at physiologically meaningful concentrations, but there is some emerging evidence suggesting it may act as a non-competitive, negative, allosteric modulator of CB 1 receptors Reference There is also a considerable body of evidence suggesting CBD also affects the activity of a significant number of other targets including ion channels, receptors, and enzymes Reference 18 Reference Reference The effects of CBD at these and other molecular targets are associated with anti-inflammatory, analgesic, anti-nausea, anti-emetic, anti-psychotic, anti-ischemic, anxiolytic, and anti-epileptiform effects Reference Reference Reference Much of what is known about the beneficial properties of the non-psychotropic cannabinoids e.
CBD, THCV is derived from in vitro and in vivo studies and few well-conducted, rigorous clinical studies of these substances exist. However, the results from these pre-clinical studies point to potential therapeutic indications such as psychosis, epilepsy, anxiety, sleep disturbances, neurodegeneration, cerebral and myocardial ischemia, inflammation, pain and immune responses, emesis, food intake, type-1 diabetes, liver disease, osteogenesis, and cancer Reference 18 Reference Reference For more in-depth information on the pharmacology of cannabinoids, the reader is invited to consult the following resources Reference 22 Reference 46 Reference 48 Reference Reference The limited information that exists is complex and requires further clarification through additional investigation.
The following paragraphs summarize the available information on this subject. Despite the limited and complex nature of the available information, it generally appears that pre-administration of CBD may potentiate some of the effects of THC through a pharmacokinetic mechanism.
Furthermore, the ratio between the two phytocannabinoids also appears to play a role in determining whether the overall effect will be of a potentiating or antagonistic nature. In one study, 24 healthy men and women who had reported using cannabis at least 10 times in their lifetime were subjected to a double-blind, placebo-controlled, mixed between- and within-subject clinical trial that showed that deliberate systematic variations in the levels of either CBD or CBC in smoked cannabis were not associated with any significant differences in any of the measured subjective, physiological, or performance tests Reference This double-blind, placebo-controlled, within-subject, crossover clinical study reported few reliable differences between the THC-only and whole-plant cannabis conditions Reference The authors further concluded that other cannabinoids present in the cannabis plant material did not alter the subjective effects of cannabis, but they speculated that cannabis samples with higher levels of cannabinoids or different ratios of the individual cannabinoids could conceivably produce different results, although no evidence to support this claim was provided in the study.
They also hypothesized that whole-plant cannabis and THC alone could differ on other outcome measures more relevant to clinical entities e. With the possible exception of one study Reference , see Section 4. Cancer Pain , which suggested differences between a whole-plant cannabis extract i. One study compared the subjective and physiological effects of oral THC to those of nabiximols in normal, healthy subjects Reference The authors reported the absence of any modulatory effect of CBD or other components of cannabis at low therapeutic cannabinoid doses, with the potential exception of the subjective "high" Reference An internet-based, cross-sectional study of 1 individuals with a consistent history of cannabis use reported that those individuals who had indicated using cannabis with a higher CBD to THC ratio had also reported experiencing fewer psychotic symptoms an effect typically associated with exposure to higher doses of THC Reference However, the authors noted that the effects were subtle.
The study was also hampered by a number of important methodological issues suggesting that the conclusions should be interpreted with caution.
The study findings are also consistent with the rest of the literature in terms of the average daily gram dose of dried cannabis used by patients i. Taken together, the study suggests that the use of cannabis containing approximately equivalent "lower" levels of THC and "higher" levels of CBD is associated with self-reported therapeutic efficacy and satisfaction across a number of different medical conditions for which dried cannabis is typically used, and also associated with attenuated levels of mood perturbation.
The evidence also suggests that cannabis containing higher levels of THC and little CBD is not necessarily more effective than lower dose strains, except for stimulation of appetite. However, the study findings suggest that the use of higher-THC strains is associated with greater mood perturbation than the lower-THC strains.
The study carried a number of caveats being that it only looked at a small number of patients, had a limited number of medical conditions and consisted of a self-reported survey.
Two in vivo studies conducted in non-human primates i. An in vivo study conducted in non-human primates i. Another in vivo study conducted in non-human primates i. Most of the available information regarding the acute and long-term effects of cannabis use comes from studies conducted on non-medical users, with much less information available from clinical studies of patients using cannabis for medical purposes.
The acute effects of smoking or eating cannabis include euphoria the marijuana "high" as well as cardiovascular, bronchopulmonary, ocular, psychological and psychomotor effects. Euphoria typically occurs shortly after smoking and generally takes longer with oral administration Reference However, some people can experience dysphoria and anxiety Reference Tachycardia is the most consistent of the acute physiological effects associated with the consumption of cannabis Reference - Reference The short-term psychoactive effects associated with cannabis smoking in non-medical users include the above-mentioned euphoria but also relaxation, time-distortion, intensification of ordinary sensory experiences such as eating, watching films, and listening to music , and loss of inhibitions that may result in laughter Reference This is followed by a depressant period Reference Driving and operation of intricate machinery, including aircraft, may be significantly impaired Reference - Reference Table 1 below , adapted from a review Reference , notes some of the pharmacological effects of cannabis in the therapeutic dosage range.
Many of the effects are biphasic, with increased activity with acute or smaller doses, and decreased activity with larger doses or chronic use Reference Reference Reference Effects differ greatly among individuals and may be greater in those who are young, severely ill, elderly, or in those taking other drugs.
See Figure 2 below for a graphical representation of the pharmacokinetics of THC. Pharmacokinetics of THC and other cannabinoids. Figure adapted from Reference THC and other cannabinoids can be administered by inhalation e. The concentration of THC and other cannabinoids in the extracellular water varies depending on serum protein binding lipoproteins, albumin , tissue storage fat, protein , metabolism hepatic microsomal, non-microsomal, extrahepatic , biliary excretion enterohepatic recirculation and renal excretion glomerular filtration, tubular secretion, passive reabsorption.
The metabolism of THC and other cannabinoids produces metabolites which can also be found in the extracellular water. The concentration of THC in the extracellular water affects the THC and other cannabinoids concentration at the site of action. The effects of THC and other cannabinoids are observed when THC and other cannabinoids interacts with cannabinoid receptors or other targets of action. THC and other cannabinoids can also be detected in hair, saliva and sweat. Smoking cannabis results in more rapid onset of action within minutes , higher blood levels of cannabinoids, and a shorter duration of acute pharmacodynamic effects compared to oral administration Reference Smoking cannabis containing 1.
Similarly, smoking cannabis joints containing 1. Smoking a 25 mg dose of cannabis in a pipe containing 2. Smoking one cannabis cigarette mg containing 6.
Compared to the data available for absorption with smoked THC, there is far less such information available for smoked CBD.
Vapourization of cannabis has been explored as an alternative to smoking. In addition, the study reported that vapourization was well tolerated with no reported adverse effects, and was preferred over smoking by the test subjects Reference While vapourization has been reported to be amenable to self-titration as has been claimed for smoking Reference Reference , the proper use of the vapourizer for optimal administration of cannabis for therapeutic purposes needs to be established in more detail Reference Bioequivalence of vapourization compared to smoking has not been thoroughly established.
Inhalation of vapourized cannabis mg of 3. No statistically significant changes were reported for the AUC 12 hour area-under-the-curve for either morphine or oxycodone, but there appeared to be a statistically significant decrease in the C max of morphine sulfate, and a delay in the time needed to reach C max for morphine during cannabis exposure Reference One clinical study reported that vapourizing mg cannabis containing low-dose 2.
Median whole-blood C max values for hydroxy-THC were 2. A different clinical study showed that inhalation of 8 to 12 puffs of vapourized cannabis containing either 2. Plasma C max of hydroxy-THC was 5. Whereas the acute effects on the CNS and physiological effects occur within minutes by the smoking route or by vapourization Reference Reference , the acute effects proceed on a time scale of hours in the case of oral ingestion Reference Reference Acute oral administration results in a slower onset of action, lower peak blood levels of cannabinoids, and a longer duration of pharmacodynamic effects compared to smoking Reference The psychotropic effect or "high" occurs much more quickly by the smoking than by the oral route, which is the reason why smoking appears to be the preferred route of administration by many, especially among non-medical users Reference Administration of a single 2.
Twice daily dosing of dronabinol individual doses of 2. A phase I study evaluating the pharmacokinetics of three oral doses of THC 3 mg, 5 mg and 6. For those subjects who reached C max within 2 hours, the mean THC concentration was 1. A randomized, double-blind, placebo-controlled, cross-over trial that evaluated the pharmacokinetics of oral THC in 10 older patients with dementia mean age 77 years over a week period reported that median time to reach C max T max was between one and two hours with THC pharmacokinetics increasing linearly with increasing dose, but again with wide inter-individual variation Reference The mean C max after the first 0.
After the second dose of 0. Consumption of cannabis-laced brownies containing 2. Peak effects occurred 2. Modest changes in pulse and blood pressure were also noted. Tea made from dried cannabis flowering tops After oral administration of chocolate cookies containing 40 mg CBD in healthy human subjects, mean plasma CBD levels ranged between 1. Oral intake of 5. While cannabinoids are lipophilic and anecdotal evidence suggests that cannabinoids dissolve better in fats and oils, the influence of various fats on cannabinoid absorption in vivo has been poorly studied.
The absolute bioavailability of THC was 2. Furthermore, an in vitro lipolysis model was used to assess the mechanism by which lipids could enhance the bioavailability of THC and CBD. Chylomicrons act as carriers in the intestine and potentially transfer THC and CBD to the systemic circulation via the intestinal lymphatic system and therefore avoid hepatic first-pass metabolism, which would explain the increased bioavailability with the lipid-based formulation.
The authors concluded that administration of cannabinoids with a fatty meal or in the form of a lipid-rich cannabis-containing cookie may increase systemic exposure and therefore change the efficacy of the drug by turning a barely effective dose into a highly effective one, or even, a therapeutic dose into a toxic one.
In mice, it was shown that hexahydrocannabinols could, as is typically observed with THC, produce cataleptogenic effects Reference The clinical implications of this conversion of CBD to THC and hexahydrocannabinols are the subject of heated debate and currently unclear. A randomized, double-blind, placebo-controlled, double-dummy, cross-over clinical study examined the pharmacokinetics of THC and its phase I and II metabolites between frequent and occasional cannabis smokers after smoked, vapourized and oral cannabis administration Reference Cannabis plant material mg containing 6.
Cannabis was administered orally by ingestion of cannabis-containing brownies. Mean T max was 7 min smoking , 5 min vapourization , and 2. Mean T max was 7 min smoking , 7 min vapourization , and 2. Mean T max was 13 min smoking , 11 min vapourization , and 2.
Mean T max was 13 min smoking , 6 min vapourization , and 2. These findings suggest, among other things, that peak blood THC concentration THC C max was significantly lower after oral consumption compared to either route of inhalation and time to peak blood THC concentration T max occurred significantly later for oral consumption compared to inhalation for both frequent and occasional cannabis smokers.
In addition, C max was significantly higher for the smoking route compared to vapourization, but only among frequent cannabis smokers. In addition, THC C max values were significantly greater among frequent smokers compared to occasional smokers after smoking and vapourization only, and hydroxy-THC C max values were significantly greater among frequent smokers regardless of route of administration.
Oro-mucosal administration of nabiximols is also amenable to self-titration Reference Reference Reference Reference In humans, rectal doses of 2.
Cannabinoids are highly hydrophobic, making transport across the aqueous layer of the skin the rate-limiting step in the diffusion process Reference No clinical studies have been published regarding the percutaneous absorption of cannabis-containing ointments, creams, or lotions. However, some pre-clinical research has been carried out on transdermal delivery of synthetic and natural cannabinoids using a dermal patch Reference Reference Due to its lipophilicity, it is taken up primarily by fatty tissues and highly perfused organs such as the brain, heart, lung, and liver Reference The apparent average volume of distribution of CBD is Pre-clinical studies in mice suggest a more rapid penetration of hydroxy-THC into the brain compared to the parent compound, on the order of 6: This finding lends further support to the evidence on the distribution, accumulation, and storage of THC and metabolites in the adipose tissue and the slow release of THC and metabolites from adipose tissue stores back into the bloodstream Reference Residual THC in plasma likely coming from bodily adipose stores detected weeks after last smoking episode may be associated with persisting psychomotor impairment in frequent chronic cannabis smokers according to the study authors Reference Most cannabinoid metabolism occurs in the liver, and different metabolites predominate depending on the route of administration Reference 78 Reference CBD undergoes extensive Phase I metabolism, with a reported 30 different metabolites in the urine, and the most abundant metabolites are hydroxylated 7 or 11 -carboxy derivatives of CBD, with 7 or 11 -hydroxy CBD as a minor metabolite Reference 78 Reference Reference Xenobiotics are not only metabolized by CYPs but they also modulate the expression level and activity of these enzymes; CYPs are therefore a focal point in drug-drug interactions and adverse drug reactions Reference Please see Section 6.
While few clinical studies have specifically sought to evaluate cannabis-drug interactions per se, many, if not most, studies investigating the therapeutic effects of cannabis e. Cannabis smoking, as well as orally administered dronabinol may also affect the pharmacokinetics of anti-retroviral medications, although no clinically significant short-term impacts on anti-retroviral effects were noted Reference In addition, and as seen with tobacco smoke, cannabis smoke has the potential to induce CYP1A2 thereby increasing the metabolism of xenobiotics biotransformed by this isozyme such as theophylline Reference or the anti-psychotic medications clozapine or olanzapine Reference Further detailed information on drug-drug interactions can be found in Section 6.
Similar results were obtained with intravenous THC administration Reference Following oxidation, the phase II metabolites of the free drug or hydroxylated-THC appear to be glucuronide conjugates Reference Peak plasma values of the psycho-inactive metabolite, norcarboxy THC, occur 1.
The plasma levels of active hydroxy metabolite, achieved through oral administration, are about three times higher than those seen with smoking Reference Concentrations of both parent drug and metabolite peak between approximately 2 to 4 h after oral dosing, and decline over several days Reference A study that characterized cannabinoid elimination in blood from 30 male daily cannabis smokers during monitored sustained abstinence for up to 33 days on a closed residential unit found that low levels approx.
Following oral administration, THC and its metabolites are also excreted in both the feces and the urine Reference 78 Reference A large portion of administered CBD is excreted intact or as its glucuronide Reference Reference Reference The variability in terminal half-life measurements are related to the dependence of this measure on assay sensitivity, as well as on the duration and timing of blood measurements Reference Low levels of THC metabolites have been detected for more than five weeks in the urine and feces of cannabis users Reference Like THC, the decline of CBD levels is also multi-phasic, and the half-life of CBD in humans after smoking has been estimated at 27 - 35 h, and 2 - 5 days after oral administration Reference Reference Reference More limited information is available for inhaled cannabis Reference 58 Reference A dosing interval of 1 h with this dose would give a "continuous high", and the recovery time after the last dose would be min i.
One clinical study reported a peak increase in heart rate and perceived "good drug effect" within 7 min after test subjects smoked a 1 g cannabis cigarette containing either 1. Compared to the placebo, both doses yielded statistically significant differences in subjective and physiological measures; the higher dose was also significantly different from the lower dose for subjective effects, but not physiological effects such as an effect on heart rate.
The equilibration half-life estimate for heart rate was approximately 7 min, but varied between 39 and 85 min for various CNS parameters Reference According to this model, the effects on the CNS developed more slowly and lasted longer than the effect on heart rate. Subjects reported smoking a mean of one joint per day in the previous 14 days prior to the initiation of the study range: During the study, subjects smoked one cannabis cigarette mean weight 0.
According to the authors of the study, the pharmacodynamic-pharmacokinetic relationship displayed a counter-clockwise hysteresis i. THC , the pharmacological effect is greater at a later time point than at an earlier one for all measured subjective effects e. This particular kind of relationship demonstrates a lack of correlation between blood concentrations of THC and observed effects, beginning immediately after the end of smoking and continuing during the initial distribution and elimination phases.
Following the start of cannabis smoking, heart rate increased significantly at the 30 min time point, diastolic blood pressure decreased significantly only from the 30 min to 1 h time point, and systolic blood pressure and respiratory rate were unaffected at any time. A study that examined the acute subjective effects associated with smoked cannabis at three different doses i. In addition, the study also showed that higher doses of THC were associated with longer duration of subjective effects.
Findings from the study showed that the time required to reach a maximal "high" rating was slightly delayed 11 - 16 min compared to the time required to reach the peak THC serum concentration.
The "high" rating declined after reaching the peak within the first 3. Scores on the VAS for "dizziness", "dry mouth", "palpitations", "impaired memory and concentration", "down", "sedated", and "anxious feelings" reached a maximum within the first 2 h post-dose and these effects were dose-dependent. With a dose of Respondents who had used cannabis in their lifetime but were not current users showed similar but less pronounced associations, indicating that the protective effect of cannabis fades with time.
The research emerging about the interplay between cannabinoids and insulin regulation may lead to some major breakthroughs in the prevention of obesity and type 2 diabetes. A study that measured data from 4, participants on the effect of cannabis on metabolic systems compared non-users to current and former users. Linked to diet and lifestyle, atherosclerosis is common in developed Western nations and can lead to heart disease or stroke.
It is a chronic inflammatory disorder involving the progressive depositing of atherosclerotic plaques immune cells carrying oxidized LDL or low-density lipoproteins.
A growing body of evidence suggests that endocannabinoid signaling plays a critical role in the pathology of atherogenesis. Studies have demonstrated that inflammatory molecules stimulate the cycle leading to atherosclerotic lesions. The CB2 receptor is also stimulated by plant-based cannabinoids.
Reduced Risk of Cancer Could cannabidiol help prevent tumors and other cancers before they grow? A study showed that animals treated with CBD were significantly less likely to develop colon cancer after being induced with carcinogens in a laboratory.
Continuing research is focused on the best ratio of CBD to THC and the most effective dose level in cancer prevention and treatment. Cannabinoids are neuroprotective, meaning that they help maintain and regulate brain health. The effects appear to be related to several actions they have on the brain, including the removal of damaged cells and the improved efficiency of mitochondria.
Extra glutamate, which stimulates nerve cells in the brain to fire, causes cells to become over-stimulated, ultimately leading to cell damage or death. Thus, cannabinoids help protect brain cells from damage, keeping the organ healthy and functioning properly.
CBD has also been shown to have an anti-inflammatory effect on the brain. As the brain ages, the creation of new neurons slows down significantly. In order to maintain brain health and prevent degenerative diseases, new cells need to be continuously created. A study showed that low doses of CBD- and THC-like cannabinoids encouraged the creation of new nerve cells in animal models, even in aging brains. Cannabinoids are facilitative of the process of bone metabolism—the cycle in which old bone material is replaced by new at a rate of about 10 percent per year, crucial to maintaining strong, healthy bones over time.
CBD in particular has been shown to block an enzyme that destroys bone-building compounds in the body, reducing the risk of age-related bone diseases like osteoporosis and osteoarthritis. In both of those diseases, the body is no longer creating new bone and cartilage cells. CBD helps spur the process of new bone-cell formation, which is why it has been found to speed the healing of broken bones and, due to a stronger fracture callus, decrease the likelihood of re-fracturing the bone bones are 35—50 percent stronger than those of non-treated subjects.
Protects and Heals the Skin The skin has the highest amount and concentration of CB2 receptors in the body. When applied topically as an infused lotion, serum, oil, or salve, the antioxidant a more powerful antioxidant than vitamins E and C  in CBD oil has many benefits and can repair damage from free radicals like UV rays and environmental pollutants.
Cannabinoid receptors can be found in the skin and seem to be connected to the regulation of oil production in the sebaceous glands. In fact, historical documents show that cannabis preparations have been used for wound healing in both animals and people in a range of cultures spanning the globe and going back thousands of years.
The use of concentrated cannabis and CBD oils to benefit and treat skin cancer is gaining popularity with a number of well-documented cases of people curing both melanoma and carcinoma-type skin cancers with the topical application of CBD and THC products. Best known is the case of Rick Simpson, who cured his basal cell carcinoma with cannabis oil and now has a widely distributed line of products.
Cannabis applied topically is not psychoactive. Cannabinoids have been proven to have an anti-inflammatory effect in numerous studies. CBD engages with the endocannabinoid system in many organs throughout the body, helping to reduce inflammation systemically.
The therapeutic potential is impressively wide-ranging, as inflammation is involved in a broad spectrum of diseases. The oral use of cannabis and CBD for anxiety appears in a Vedic text dated around BCE, and it is one of the most common uses of the plant across various cultures.
While THC can increase anxiety in some patients, it lowers it in others. However, CBD effects have been shown to consistently reduce anxiety when present in higher concentrations in the cannabis plant. On its own, CBD has been shown in a number of animal and human studies to lessen anxiety. The stress-reducing effect appears to be related to activity in both the limbic and paralimbic brain areas. A research review assessed a number of international studies and concluded that CBD has been shown to reduce anxiety , and in particular social anxiety, in multiple studies and called for more clinical trials.
It is suggested that patients work with a health care practitioner experienced in recommending cannabidiol or medicinal cannabis so that dosage and delivery methods can be developed and fine-tuned on an individual basis. At the same time, educated and aware patients can be their own highly informed health consultants. For anxiety, CBD products with a ratio of High-CBD cannabinoids can be very effective in reducing chronic anxiety, treating temporary stress, and protecting the body from the physiological effects of both.
Varieties high in linalool, a terpene shared with lavender, are known to be effective for relieving anxiety. Always start with the micro dose to test sensitivity and go up as needed within the dosing range, before going to the next, until symptoms subside.
The micro to standard dose is usually recommended to treat stress and anxiety with CBD. For relief of immediate symptoms, as in a panic or anxiety attack, vaporizing or smoking work well. The medication lasts one to three hours, whereas most ingested products, including CBD oil, take thirty to sixty minutes before taking effect and last six to eight hours.
Herbal vaporizers that use the whole plant are also an effective delivery method. Sublingual sprays or tinctures taken as liquid drops take effect quickly and last longer than inhaled products. The Cannabis Health Index CHI is an evidence-based scoring system for cannabis in general, not just CBD oil effects and its effectiveness on various health issues based on currently available research data.
Using this rubric and based on eleven studies, cannabis rated in the possible-to-probable range of efficacy for treatment of anxiety. Elixinol Organic High Potency CBD Capsules Elixinol offers a highly concentrated, high-potency, organic whole-hemp plant CBD oil , which is naturally extracted with carbon dioxide and free of all synthetics and chemicals. Whole-hemp plant extracts contain synergistic compounds that are believed to enhance the effectiveness and benefits of CBD.
Clinical depression is a serious mood disorder characterized by persistent sadness and loss of interest, sometimes leading to decreased appetite and energy and suicidal thoughts. Retrieved June 2, Retrieved 19 October Retrieved 1 January Retrieved 1 February Annales de Toxicologie Analytique in French. Swedish Medical Products Agency. Retrieved 31 July BBC News - Health. Retrieved 8 February Retrieved May 20, Is Cannabidiol the Answer for Disorders of Motivation? Annual Review of Neuroscience.
Williams, Alex October 27, The New York Times. Articles related to Cannabidiol. Recreational and medical applications rights Industrial applications. Autoflowering cannabis Cannabis indica ruderalis sativa Difference between C. Medical cannabis History Timeline Religious and spiritual use Chalice.
Cannabis in pregnancy Dependence Effects of cannabis Long-term Endocannabinoid system Impaired driving. Adult lifetime use by country Annual use by country. Return to class B Uruguay: Decriminalization of non-medical use Rescheduling per the Controlled Substances Act. Cannabis political parties List of British politicians who have acknowledged cannabis use List of American politicians who have acknowledged cannabis use.
ADPF Gonzales v. United States thermal imaging Leary v. Cannabis portal Hemp portal Category. Cannabinoid receptor modulators cannabinoids by pharmacology List of: Analgesics N02A , N02B. Meclofenamic acid Mefenamic acid. Cannabidiol Cannabis Nabilone Nabiximols Tetrahydrocannabinol dronabinol. Gabapentin Gabapentin enacarbil Pregabalin Ziconotide.
Carbamazepine Lacosamide Local anesthetics e. Bromide potassium bromide , sodium bromide Imepitoin Paraldehyde Stiripentol. Fatty acids and related: Valproate Valpromide Valproate pivoxil Vigabatrin. Progabide ; GAT-1 inhibitors: Ethotoin Fosphenytoin Mephenytoin Phenytoin ; Ureides: Valproate Valpromide Valproate pivoxil ; Carboxamides: Carbamazepine Eslicarbazepine acetate Oxcarbazepine ; Others: Lacosamide Lamotrigine Rufinamide Topiramate Zonisamide.
Ethadione Paramethadione Trimethadione ; Succinimides: Ethosuximide Mesuximide Phensuximide ; Gabapentinoids: Gabapentin Pregabalin ; Others: Imepitoin Lamotrigine Topiramate Zonisamide. Acetazolamide Ethoxzolamide Sultiame Topiramate Zonisamide. Agonists abridged; see here for more: Agonists abridged; see here for a full list: AR-A Beta blockers e. Agomelatine Atypical antipsychotics e.
Green Relief Blog Cannabis Oil Dosage Guide. As we've blogged before, Graphic illustration of the flower to oil ratio. All cannabis oil. CBD-rich cannabis oil products can be taken sublingually, orally (as edibles or gel caps) CBD can lessen the mind-altering effects of THC, so, a greater ratio of. The and are high CBD, low THC, and rarely psychoactive. These ratios are ideal for novice cannabis users or people who don't want.