# _Cannabis sativa_ L. as a Natural Drug Meeting the Criteria of a Multitarget Approach to Treatment
## 4 Pharmacological Application
### Epilepsy  
Epilepsy is believed to be the most common noninfectious neurological disease. Moreover, one-third of patients suffer from seizures resistant to standard antiepileptic drugs. Antiepileptic drugs have been used for over 160 years. They prevent seizures, but there is no evidence that they have disease-modifying properties. They affect the mechanisms causing the brain's excitability. Antiepileptic drugs disrupt the creation and spread of epileptic hyperactivity. These drugs act on the following mechanisms: (i) modulation of voltage-dependent sodium channels (carbamazepine and phenytoin), calcium channels (ethosuximide), and potassium channels (retigabine and ezogabine); (ii) enhancement of inhibited GABA transmission (benzodiazepepines, tiagabine, and vigabatrin); (iii) weakening of the stimulant glutamate transmission (perampanel); and (iv) presynaptic modification of neurotransmitter release (levetiracetam, brivaracetam, gabapentin, and pre-gabalin) [99]. Drugs introduced before 1989 are called \"first-generation\" drugs, and those introduced later are named \"second-generation\" drugs. Medicines that have been recently approved (brivaracetam, eslicarbazepine acetate, lacosamide, perampanel, rufinamide, and stiripentol) that are improvements to classic drugs or rely on novel mechanisms are called \"third-generation\" drugs [100]. Since 2018, the last group has also included CBD. Drug-resistant epilepsy is diagnosed when symptom control cannot be achieved despite the use of at least two different antiepileptic drugs in an appropriate dose [101]. Epilepsy with the greatest resistance to treatment includes LGS, DS, fever-related epilepsy syndrome, and epilepsy in tuberous sclerosis syndrome (TSC) [102]. The patient's quality of life and cognitive and psychosocial problems significantly deteriorate. Due to the occurrence of drug-resistant epilepsy and severe side effects associated with the use of traditional antiepileptic drugs, preparations with higher safety and effectiveness are being sought. The antiepileptic use of _Cannabis_ dates back to ancient times. It is generally accepted that _Cannabis_ benefits in anticonvulsant therapy are linked to CBD. However, the mechanism of CBD action in the treatment of epilepsy is not fully understood. The orphan G-protein coupled receptor, GPR\({}_{55}\) antagonism, is mentioned as the mechanism. Recent studies have shown that CBD significantly reduces the number of seizures. Moreover, it seems that only mild side effects occur. Among these, increased liver enzymes levels are improved with a continuity of therapy or by dose reduction. However, it should be emphasized that CBD is most often used in studies with standard antiepileptic therapy, so it is difficult to assess whether it has antiepileptic effects or only enhances the effects of traditional drugs [103]. The FDA approved a 99% CBD extract called Epidiolex in 2018 for the treatment of seizures associated with LGS, DS, or TSC in patients one years of age and older [104]. In recent years, there has been an increased interest in the use of _Cannabis_ as part of the treatment of childhood epilepsy, among others, due to numerous media reports on children whose symptoms improved with _Cannabis_. Many parents of children struggling with drug-resistant epilepsy turn to alternative therapeutic measures, sometimes with doctors' help and sometimes on their own [101]. A lot of attention was focused on a Colorado family who was looking for alternative treatments for a girl suffering from DS, [PERSON]. Her supportive treatment included a CBD-rich _Cannabis_ strain that was later named \"Web Charlotte.\" After three months of using it, the number of seizures dropped from 300 per week to 30 per month. However, after 20 months of treatment, the monthly number of attacks was about three, and the girl started talking and walking [104]. The effectiveness of CBD against the drug-resistant seizures that occur in DS has been studied.