By Sahana Ghosh
Kolkata, Jan 19 (IANS): In a breakthrough that could impact the blurring realms of pain and pleasure, Indian scientists have designed a potential morphine replacement, sans the side effects of addiction, but loaded with pain-killing power.

For nearly four millennia, morphine and its cousin compounds (opioids) have ruled the roost in terms of their extraordinary prowess to dull pain (analgesics).

Morphine (sulphate) is a by-product of opium which is extracted from poppy plants. India grows poppy under licence in three states - Uttar Pradesh, Madhya Pradesh and Rajasthan.

It is sheer irony that India is the world's largest legal exporter of morphine sulphate when stringent laws and regulations aimed to curb its misuse in the country limits access to only 0.4 percent of the population in need, i.e. a million people with cancer and an unknown number of people with other incurable and disabling diseases.

Morphine works by binding to the opioid category of receptors in the brain and is a boon for pain therapy. It is considered the drug of choice for treatment of chronic pain - due to burns, terminal pain or cancer-related pain.

It is also included in the WHO 'Model List of Essential Medicines'.

Morphine comes in different forms, such as short-acting liquids or tablets, and long-acting (sustained-release) tablets or capsules.

However, it can be a bane too, given its potential for addiction and abuse.

"Its pain relieving property is very high because of its strong binding to the opioid receptor but it also has a high risk for abuse. It has addiction property like heroin but not as strong. In addition, it may cause breathing problems," Surajit Sinha, associate professor in the organic chemistry department at the Indian Association for the Cultivation of Science in Kolkata, told IANS.

The solution, Sinha said, is to tweak compounds and create a substitute that is structurally as distinct from morphine as chalk and cheese but at the same time clings to the specific brain receptors for effective non-addictive pain therapy.

Sinha and his team considered a plant-derived compound called ibogaine, popular in African folk medicine and known for its anti-addictive properties and pain-killing effects, but notorious for its psychedelic (hallucinogenic) reaction.

It is illegal in countries like Norway and strictly regulated in the US.

"We synthesised an ibogaine analogue in our laboratory from scratch and saw that when mice was treated with 40 mg/kg dose of the new substance, it could provide pain relief for more than 50 minutes.

"When treated with morphine at a dose of 10 mg/kg, duration was 45 minutes, which is lesser than the novel substance," said Sinha.

The screening was done in collaboration with Sumantra Das's lab in the neurobiology department at the CSIR-Indian Institute of Chemical Biology in Jadavpur.

The study can be read online in the September edition of the Bio-organic and Medicinal Chemistry journal.

The researchers have applied for patent and are now working towards lowering the dose and studying other properties, including effects in the nervous system.

"For the first phase of the study, we can say the analogue is safe, indigenous and comes without the psychedelic properties. It is also completely different from morphine structurally," said Sinha.

He said there have been important discoveries in this area, particularly in the US, but a morphine replacement without side-effects still eludes drug developers.

The larger picture, according to Sinha, lies in augmenting pain therapy and palliative care in India.

M.R. Rajagopal, a leading palliative care expert, said major barriers to access to opioids are complicated regulations and problems related to attitude and knowledge regarding pain relief and opioids among professionals and the public.

"Any invention like that would be a godsend," said Rajagopal, chairman of Pallium India in Thiruvananthapuram, told IANS via email and over telephone.

Rajagopal spearheaded the procedure leading to the Amendment of Narcotic Drugs and Psychotropic Substances (NDPS) Act of India in 2014, which will help ease access to morphine-based drugs through uniform regulation across states for giving out licences to manufacture morphine-based drugs.

"A common state rule will be announced by the central government. But it has not been done yet. It is a procedural delay. Once they announce the rules, the rules will be simpler - only if the states implement it.

"Changing the law alone is not going to make a big difference unless it is implemented," said Rajagopal, who is also the director of the WHO's Collaborating Centre for Training and Policy on Access to Pain Relief.

Currently, 13 states in India and one union territory have simplified regulations, but opioid availability has improved only in a few of these states, he said.