Cannabinoids CBD and synthetic cannabinoids SC are widely used psychoactive substances nowadays. In Egypt, Nicotine 9% is the most commonly used substance over the lifetime, followed by benzodiazepines 5.1%, alcohol 3.3%, organic solvents 3.1%, and cannabis 3.1%. Sadek et al., 2002 found that 3.9 % of secondary school students in Cairo (Rabie et al.,2020) used illicit drugs. While only 0.7 % admitted to using cannabinoids (Zaky et al.,2011).
SC abuse is a hazard that affects millions of people worldwide, taking into consideration that the Egyptian population has now exceeded 104 million according to the Central Agency for Public Mobilization and Statistics (CAPMAS) (Rabie et al.,2020).
Recently, new psychoactive substances are popular in Europe and rushed to America. About 40% of web users are teens who are usually getting SC through online website, gas stations, and tobacco shops (Yeruva et al., 2019).
Synthetic cannabinoids (SCs) are a large family of chemically unrelated structures and similar to Δ 9-tetrahydrocannabinol (THC) which 9-tetrahydrocannabinol (THC), the active principle of cannabis, interacts with cannabinoid receptors (CB1 and CB2) to exert its psychoactive effects (Sobh1and Sobh 2.,2018). However, because CBD products contain little or no THC, they do not have the same psychoactive effects. CBD reduces psychosis but increases the risk of dementia and other Alzheimer’s or other cognitive illnesses as well as pain (Oberbarnscheidta and Miller., 2020).
SCs are known as SCRAs (Synthetic cannabinoid receptor agonists). SCRAs have more severe side effects than natural cannabis. SCRAs' increased tendency for developing psychotic traits is due to their high potency and the lack of CBD help (Babalonis et al., 2013).
An interesting new family of cannabis agonists is gaining traction (Department of Justice, Cairo, 2018). Chemical components and compound concentrations differ between and within packages. Strox and voodoo are the most popular SCs in Egypt. JWH-018, CP 47,497-C8, and Mister Nice Guy are structural SCB classes that are psychoactive (Hess, 2016). "Spice," "K2," "Black Mamba," and "Scooby Snax" are some of the brand names for these products (Castaneto et al.,2014 & Seely et al.,2013). Incense contains atropine and hyoscyamine, which are sprayed on marigolds, APEX SC, and AKB-48, which are now on the DEA's Schedule 1 list (Bozkurt., 2015 & Mills et al., 2015).
SC metabolites were previously reported to be present in serum, oral fluid, and hair, however novel SC had no urine metabolites. AKB48 was found in confiscated items (Uchiyama et al., 2012; Odoardi et al., 2016) and bodily fluids of people submitted to toxicological control (Uchiyama et al., 2012; Odoardi et al., 2016; Karinen et al., 2015; Vikingsson et al., 2015). SCs are a common occurrence that are undetectable by standard cannabis tests or immunoassays (Chimalakonda et al.,2011; Hutter et al.,2013; Jang et al.,2014). President Barack Obama signed the Synthetic Drug Abuse Prevention Act (SDAPA) in July 2012 (World Anti-Doping Agency.,2014).
Cannabinoids interact with various receptors, such as ion channel and nuclear receptors, despite the fact that only CB1R and CB2R are generally recognized CBRs (Kano et al.,2009, Howlett et al.,2002). SC has a stronger affinity for receptors than marijuana. SCRAs have more severe side effects than natural cannabis. The CB1R is associated to cardiovascular, digestive, neurological, and addiction diseases when it is activated in a systematic way (Volkow et al.,2016). They can harm the brain, heart, GI tract, and kidneys, among other organs (Radhakrishnan et al, 2014).
Toxicity and abuse potential of SC leads to clinical effects include arousal (19.1%), drowsiness (17.5%), hypertension (9.6%), nausea (9.3%), confusion (8.9 %), dizziness and vertigo (8.1%), and chest pain (8.1%). Insufficiency of SC can cause ischemia, MI, and hyperemesis SC and tubular necrosis (McKeever et al., 2015).
It is been linked to neuropsychiatric problems. Anxiety, psychosis, tachycardia, and seizures were all produced by SCRAs. SC can result in self-mutilation catatonia, hallucinations, or delusions (Schep et al., 2015). APEX SC causes insomnia that lasts weeks or months, as well as suicidal thoughts (Shanks et al., 2012). Apart from these dangers, long-term use of SCs has been linked to withdrawal symptoms including as agitation, anxiety, and mood swings (Nacca et al., 2013). SC can cause epilepsy, stroke-induced inattention, flexion-extension, and other nervous system issues (Musshoff et al., 2014). Anticholinergic effects include twitches and hiccups (Mir et al., 2011, Bhanushali et al., 2013).
CBD lacks neuroprotective qualities, causing cognitive decline (Demirakca et al, 2011). SC degrades both physical and mental functioning. SC patients lacked executive, memory, and visual-spatial skills. The brain changes of SC users showed cognitive impairments. They had poor executive function (Tomiyama and Funada, 2014). CB agonists like AM4054 and WIN55212-2 impact rat in two-choice reaction time, Musshoff et al., (2014) reported. Miller et al., 2013 and Basavarajappa et al., 2014 found that LTP and WM are affected by hippocampal activity in SCs. Long-term SC use may impair cognition and raise dementia risk (Lazarov and Hollands,2016).
Non-cannabinoid agonists target dopamine, opioids, and orexin-1 (CB1 and D2). Both glutamate and dopamine work. Loss of dopamine by endocannabinoids ECS may impact working memory in SC users (Egerton et al., 2006). D and glutamate levels in the brain may influence cognitive flexibility. After two weeks of therapy with a CB1 agonist as little as 0.2 mg/kg, rats' dopamine levels changed (Gomes et al., 2015). The Trial Making Test B measured speed and sequential ability in SC users to assess executive dysfunction (Cengel et al., 2018).
A DTI study indicated that SC abusers have smaller corpus callosum and thalami than healthy controls. Both the corpus callosum and the anterior thalamic radiation revealed temporal alterations. Both have an effect on mind. In recent fMRI studies, active prefrontal, basal, and parietal cortices (Cohen and Weinstein, 2018). On-task thalamic alterations in PET/fMRI. In addition to the inferior fronto-occipital fasciculus (OFC) which regulates inhibition and attention, the temporal occipital fascia and social cognitive areas are also affected (Hill et al., 2013).
This addiction's broad consequences make it tough to resist. SCs have no antidote due to their dynamic chemistry (Castellanos and Gralnik, 2015). Close supervision and supportive care treat symptoms. Psychotherapy is not the only option for academic and career preparation. Therapy helps daily skills (Cengel et al., 2018).