Tolerance to the behavioral and psychological effects of THC has been demonstrated in adolescent humans and animals. The mechanisms that create this tolerance to THC are thought to involve changes in cannabinoid receptor function.One study has shown that between 2001–2002 and 2012–2013, the use of marijuana in the US doubled.Cannabis dependence develops in about 9% of users, significantly less than that of heroin, cocaine, alcohol, and prescribed anxiolytics, but slightly higher than that for psilocybin, mescaline, or LSD. Of those who use cannabis daily, 10–20% develop dependence. Withdrawal
Cannabis withdrawal symptoms occur in one-half of people in treatment for cannabis use disorders. Symptoms may include dysphoria (anxiety, irritability, depression, restlessness), disturbed sleep, gastrointestinal symptoms, and decreased appetite. It is often paired with rhythmic movement disorder. Most symptoms begin during the first week of abstinence and resolve after a few weeks. About 12% of heavy cannabis users showed cannabis withdrawal as defined by the DSM-5, and this was associated with significant disability as well as mood, anxiety and personality disorders. Cause
Cannabis addiction is often due to prolonged and increasing use of the drug. Increasing the strength of the cannabis taken and an increasing use of more effective methods of delivery often increase the progression of cannabis dependency. It can also be caused by being prone to becoming addicted to substances, which can either be genetically or environmentally acquired.
Although some cases have been reported, there is not enough evidence to indicate an association between Cowden syndrome and the development of male breast cancer. Up to 75% demonstrate benign breast conditions such as intraductal papillomatosis, fibroadenomas, and fibrocystic changes. However, there is currently not enough evidence to determine if benign breast disease occurs more frequently in Cowdens patients as compared to individuals without a hereditary cancer syndrome.Central Nervous System
Macrocephaly is observed in 84% of patients with Cowden syndrome. It typically occurs due to an abnormally enlarged brain, or megalencephaly. Patients may also exhibit dolichocephaly. Varying degrees of autism spectrum disorder and intellectual disability have been reported as well. Lhermitte-Duclos disease is a benign cerebellar tumor that typically does not manifest until adulthood in patients with Cowden syndrome. Genetics
Cowden syndrome is inherited in an autosomal dominant fashion. Germline mutations in PTEN (phosphatase and tensin homolog), a tumor suppressor gene, are found in up to 80% of Cowdens patients. Several other hereditary cancer syndromes, such as Bannayan-Riley-Ruvalcaba syndrome, have been associated with mutations in the PTEN gene as well. PTEN negatively regulates the cytoplasmic receptor tyrosine kinase pathway, which is responsible for cell growth and survival, and also functions to repair errors in DNA. Thus, in the absence of this protein, cancerous cells are more likely to develop, survive, and proliferate.Recently, it was discovered that germline heterozygous mutations in SEC23B, a component of coat protein complex II vesicles secreted from the endoplasmic reticulum, are associated with Cowden syndrome.