Cryptorchidism is a very common anomaly of the male genitalia, affecting 2%-4% of male infants and is more common in premature infants. There are two separate stages of testicular descent. The first stage occurs at 8-15 weeks' gestation in the human fetus and is characterized by enlargement of the genito-inguinal ligament, or gubernaculum, and regression of the cranial suspensory ligament. The testis remains close to the future inguinal region as the fetal abdomen grows. Leydig cells in the testis produce insulin-like hormone 3, which stimulates the caudal gubernaculum to grow and become thicker. Mullerian inhibiting substance may have a role in the first phase of descent by stimulating the swelling reaction in the gubernaculum. The second phase of testicular descent requires migration of the gubernaculum and testis from the inguinal region to the scrotum, between 25 and 35 weeks' gestation. The genitofemoral nerve releases calcitonin gene-related peptide, a neurotransmitter that provides a chemotactic gradient to guide migration. The exact cause of cyrptorchidism remains elusive. Information is mainly derived from animal studies (especially in rodents), which may not extrapolate to the human setting. These findings, however, do have some similarities among mammalian species. The current recommended timing for orchidopexy is between 6 and 12 months of life in an effort to preserve the spermatogonia--the stem cells for subsequent spermatogenesis. Despite surgical treatment by orchidopexy, the long-term outcome still remains problematic and controversial. Impaired fertility (33% in unilateral cases and 66% in bilateral undescended testes) and a cancer risk 5-10 times greater than normal is observed over time. Further research into the cause and management of undescended testes is necessary.

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The Australian Federal Government legalised access to medicinal cannabis in 2016. More than 100 different cannabis products are now available to prescribe. Most are oral preparations (oils) or capsules containing delta-9-tetrahydrocannabinol or cannabidiol. Driedflower products are also available. As most products are unregistered drugs, prescribing requires approval under the Therapeutic Goods Administration Special Access Scheme-B or Authorised Prescriber Scheme. Special Access Scheme Category B applications can be made online, with approval usually being given within 24-48 hours. However, supply chain problems may delay dispensing by the pharmacy. By the end of 2019, over 28,000 prescribing approvals had been issued to patients, involving more than 1400 doctors, mostly GPs. More than 70,000 approvals are projected by the end of 2020. Most prescriptions are for chronic non-cancer pain, anxiety, cancer-related symptoms, epilepsy and other neurological disorders. However, the evidence supporting some indications is limited. Many doctors are cautious about prescribing cannabis. While serious adverse events are rare, there are legitimate concerns around driving, cognitive impairment and drug dependence with products containing delta-9-tetrahydrocannabinol. Cannabidiol-only products pose fewer risks. What is medicinal cannabis? The cannabis plant contains hundreds of bioactive molecules, most of which are as yet uncharacterised. The two best studied cannabinoids are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is responsible for the intoxicating effects of cannabis due to its action on CB1 cannabinoid receptors. 6 Despite intoxicating effects at higher doses, clinical trial evidence generally supports the efficacy of THC in treating conditions such as chronic pain, spasticity in multiple sclerosis, anorexia and cachexia, Tourette syndrome and chemotherapyinduced nausea and vomiting. 7,8 Trials currently underway will help to better define the role of THC as a therapeutic across these and other conditions. 9,10 CBD has a very wide range of pharmacological actions but no intoxicating effects. Early evidence suggests therapeutic actions of CBD at relatively high doses (300-1500 mg) in treating epilepsy, anxiety and psychosis. 11-13 Numerous clinical trials are underway for other conditions such as neuropathic pain, drug and alcohol dependence and neurodegenerative disorders. In many countries, CBD is readily available in over-thecounter nutraceutical 'wellness' products. These contain very low doses (e.g. 5-25 mg) for which there is little current evidence of health benefits. Over-the-counter access to CBD is not yet available in Australia, although Jonathon C Arnold Deputy academic director, Lambert Initiative for Cannabinoid Therapeutics, Brain and Mind Centre 1

Testicular descent to the scrotum involves complex anatomical rearrangements and hormonal regulation. The gubernaculum remains the key structure, undergoing the 'swelling reaction' in the transabdominal phase, and actively migrating out of the abdominal wall to the scrotum in the inguinoscrotal phase. Insulin-like hormone 3 (Insl3) is the primary regulator of the first phase, possibly augmented by Müllerian inhibiting substance/anitmüllerian hormone (MIS/AMH), and regression of the cranial suspensory ligament by testosterone. The inguinoscrotal phase is controlled by androgens acting both directly on the gubernaculum and indirectly via the genitofemoral nerve, and release of calcitonin gene-related peptide from its sensory fibres. Outgrowth of the gubernaculum and elongation to the scrotum has many similarities to an embryonic limb bud.Cryptorchidism occurs because of both failure of migration congenitally, and failure of elongation of the spermatic cord postnatally. Germ cell development postnatally is disturbed in congenital cryptorchidism, but our current understanding of germ cell biology suggests that early orchidopexy, around 6 months of age, should provide a significant improvement in prognosis compared with a previous generation. Hormone treatment is not currently recommended. Acquired cryptorchid testes may need orchidopexy once they no longer reach the scrotum, although this remains controversial.