Though cannabis is biologically classified as the single species Cannabis Sativa, there are at least three distinct plant varieties: Cannabis Sativa, Cannabis Indica, and Cannabis Ruderalis, though the last is rare. There are also hybrids, which are crosses between sativa and indica varieties. Cannabis used for fiber is typically referred to as hemp and has only small amounts of the psychoactive cannabinoid THC, usually less than 1%. Genetic “breeders” of the cannabis seed have developed thousands of different strains of cannabis from these three varieties. There are marked differences between sativa, indica, and hybrid. Today, we mostly find hybrids. It can be difficult to find pure indica or sativa.All types of medical cannabis produce effects that are more similar than not, including pain and nausea control, appetite stimulation, reduced muscle spasm, improved sleep, and others. But individual strains will have differing cannabinoid and terpene content, producing noticeably different effects. Many people report finding some strains more beneficial than others. For instance, strains with more CBD tend to produce better pain and spasticity relief. As noted above, effects will also vary for an individual based on the setting in which it is used and the person's physiological state when using it.
In general, sativas and indicas are frequently distinguished as follows:
The primary effects are on thoughts and feelings. Sativas tend to produces stimulating feelings, and many prefer it for daytime use. Some noted therapeutic effects from use of Sativas:
Increased sense of well-being, focus, creativity
Reduces depression, elevates mood
Some noted Side-Effects from use of Sativas
Increased anxiety feelings
Increased paranoia feelings
The primary effects are on the body. Indicas tend to produce sedated feelings, and many prefer it for nighttime use.
Some noted Therapeutic Effects from use of Indicas:
Provides relaxation/reduces stress
Reduces nausea, stimulates appetite
Reduces intra-ocular pressure
Reduces seizure frequency/anti-convulsant
Some noted side-effects from use of Indicas:
Feelings of tiredness
Strains bred from crossing two or more varieties, with typically one dominant. For example, a sativa-dominant cross may be helpful in stimulating appetite and relaxing muscle spasms. Crosses are reported to work well to combat nausea and increase appetite.Cannabinoids are a group of 21-carbon–containing terpenophenolic compounds produced uniquely by Cannabis species (e.g., Cannabis sativa L.) .These plant-derived compounds may be referred to as phytocannabinoids. Although delta-9-tetrahydrocannabinol (THC) is the primary psychoactive ingredient, other known compounds with biologic activity are cannabinol, cannabidiol (CBD), cannabichromene, cannabigerol, tetrahydrocannabivarin, and delta-8-THC. CBD, in particular, is thought to have significant analgesic and anti-inflammatory activity without the psychoactive effect (high) of delta-9-THC.
One study in mice and rats suggested that cannabinoids may have a protective effect against the development of certain types of tumors. During this 2-year study, groups of mice and rats were given various doses of THC by gavage. A dose-related decrease in the incidence of hepatic adenoma tumors and hepatocellular carcinoma (HCC) was observed in the mice. Decreased incidences of benign tumors (polyps and adenomas) in other organs (mammary gland, uterus, pituitary, testis, and pancreas) were also noted in the rats. In another study, delta-9-THC, delta-8-THC, and cannabinol were found to inhibit the growth of Lewis lung adenocarcinoma cells in vitro and in vivo .In addition, other tumors have been shown to be sensitive to cannabinoid-induced growth inhibition.
Cannabinoids may cause antitumor effects by various mechanisms, including induction of cell death, inhibition of cell growth, and inhibition of tumor angiogenesis invasion and metastasis. Two reviews summarize the molecular mechanisms of action of cannabinoids as antitumor agents. Cannabinoids appear to kill tumor cells but do not affect their nontransformed counterparts and may even protect them from cell death. For example, these compounds have been shown to induce apoptosis in glioma cells in culture and induce regression of glioma tumors in mice and rats, while they protect normal glial cells of astroglial and oligodendroglial lineages from apoptosis mediated by the CB1 receptor.
The effects of delta-9-THC and a synthetic agonist of the CB2 receptor were investigated in HCC. Both agents reduced the viability of HCC cells in vitro and demonstrated antitumor effects in HCC subcutaneous xenografts in nude mice. The investigations documented that the anti-HCC effects are mediated by way of the CB2 receptor. Similar to findings in glioma cells, the cannabinoids were shown to trigger cell death through stimulation of an endoplasmic reticulum stress pathway that activates autophagy and promotes apoptosis. Other investigations have confirmed that CB1 and CB2 receptors may be potential targets in non-small cell lung carcinoma and breast cancer.
An in vitro study of the effect of CBD on programmed cell death in breast cancer cell lines found that CBD induced programmed cell death, independent of the CB1, CB2, or vanilloid receptors. CBD inhibited the survival of both estrogen receptor–positive and estrogen receptor–negative breast cancer cell lines, inducing apoptosis in a concentration-dependent manner while having little effect on nontumorigenic mammary cells. Other studies have also shown the antitumor effect of cannabinoids (i.e., CBD and THC) in preclinical models of breast cancer.
CBD has also been demonstrated to exert a chemopreventive effect in a mouse model of colon cancer. In this experimental system, azoxymethane increased premalignant and malignant lesions in the mouse colon. Animals treated with azoxymethane and CBD concurrently were protected from developing premalignant and malignant lesions. In in vitro experiments involving colorectal cancer cell lines, the investigators found that CBD protected DNA from oxidative damage, increased endocannabinoid levels, and reduced cell proliferation. In a subsequent study, the investigators found that the antiproliferative effect of CBD was counteracted by selective CB1 but not CB2 receptor antagonists, suggesting an involvement of CB1 receptors.
Another investigation into the antitumor effects of CBD examined the role of intercellular adhesion molecule-1 (ICAM-1). ICAM-1 expression has been reported to be negatively correlated with cancer metastasis. In lung cancer cell lines, CBD upregulated ICAM-1, leading to decreased cancer cell invasiveness.
In an in vivo model using severe combined immunodeficient mice, subcutaneous tumors were generated by inoculating the animals with cells from human non-small cell lung carcinoma cell lines.Tumor growth was inhibited by 60% in THC-treated mice compared with vehicle-treated control mice. Tumor specimens revealed that THC had antiangiogenic and antiproliferative effects. However, research with immunocompetent murine tumor models has demonstrated immunosuppression and enhanced tumor growth in mice treated with THC.
In addition, both plant-derived and endogenous cannabinoids have been studied for anti-inflammatory effects. A mouse study demonstrated that endogenous cannabinoid system signaling is likely to provide intrinsic protection against colonic inflammation.As a result, a hypothesis that phytocannabinoids and endocannabinoids may be useful in the risk reduction and treatment of colorectal cancer has been developed.
CBD may also enhance uptake of cytotoxic drugs into malignant cells. Activation of the transient receptor potential vanilloid type 2 (TRPV2) has been shown to inhibit proliferation of human glioblastoma multiforme cells and overcome resistance to the chemotherapy agent carmustine. In an in vitro model, CBD increased TRPV2 activation and increased uptake of cytotoxic drugs, leading to apoptosis of glioma cells without affecting normal human astrocytes. This suggests that coadministration of CBD with cytotoxic agents may increase drug uptake and potentiate cell death in human glioma cells. Also, CBD together with THC may enhance the antitumor activity of classic chemotherapeutic drugs such as temozolomide in some mouse models of cancer.
Many animal studies have previously demonstrated that delta-9-THC and other cannabinoids have a stimulatory effect on appetite and increase food intake. It is believed that the endogenous cannabinoid system may serve as a regulator of feeding behavior. The endogenous cannabinoid anandamide potently enhances appetite in mice. Moreover, CB1 receptors in the hypothalamus may be involved in the motivational or reward aspects of eating.
Understanding the mechanism of cannabinoid-induced analgesia has been increased through the study of cannabinoid receptors, endocannabinoids, and synthetic agonists and antagonists. The CB1 receptor is found in both the central nervous system (CNS) and in peripheral nerve terminals. Similar to opioid receptors, increased levels of the CB1 receptor are found in regions of the brain that regulate nociceptive processing. CB2 receptors, located predominantly in peripheral tissue, exist at very low levels in the CNS. With the development of receptor-specific antagonists, additional information about the roles of the receptors and endogenous cannabinoids in the modulation of pain has been obtained.
Cannabinoids may also contribute to pain modulation through an anti-inflammatory mechanism; a CB2 effect with cannabinoids acting on mast cell receptors to attenuate the release of inflammatory agents, such as histamine and serotonin, and on keratinocytes to enhance the release of analgesic opioids has been described. One study reported that the efficacy of synthetic CB1- and CB2-receptor agonists were comparable with the efficacy of morphine in a murine model of tumor pain.
Cannabis and Cannabinoids
Because cannabinoid receptors, unlike opioid receptors, are not located in the brainstem areas controlling respiration, lethal overdoses from Cannabis and cannabinoids do not occur.However, cannabinoid receptors are present in other tissues throughout the body, not just in the central nervous system, and adverse effects include tachycardia, hypotension, conjunctival injection, bronchodilation, muscle relaxation, and decreased gastrointestinal motility.
Although cannabinoids are considered by some to be addictive drugs, their addictive potential is considerably lower than that of other prescribed agents or substances of abuse. The brain develops a tolerance to cannabinoids.
Withdrawal symptoms such as irritability, insomnia with sleep electroencephalogram disturbance, restlessness, hot flashes, and, rarely, nausea and cramping have been observed. However, these symptoms appear to be mild compared with withdrawal symptoms associated with opiates or benzodiazepines, and the symptoms usually dissipate after a few days.
Unlike other commonly used drugs, cannabinoids are stored in adipose tissue and excreted at a low rate (half-life 1–3 days), so even abrupt cessation of cannabinoid intake is not associated with rapid declines in plasma concentrations that would precipitate severe or abrupt withdrawal symptoms or drug cravings.
Since Cannabis smoke contains many of the same components as tobacco smoke, there are valid concerns about the adverse pulmonary effects of inhaledCannabis. A longitudinal study in a noncancer population evaluated repeated measurements of pulmonary function over 20 years in 5,115 men and women whose smoking histories were known. While tobacco exposure was associated with decreased pulmonary function, the investigators concluded that occasional and low-cumulative Cannabis use was not associated with adverse effects on pulmonary function.