Sands Cymru, Drugaid Cymru and Dash, are launching an initiative on Wednesday to tackle the problem.
Sands Cymru chief executive Ifor Glyn said: "This is not a problem that's going to go away anytime soon."
Public Health Wales has previously noted a "substantial escalation" in use since 2010.
Sands said the blanket ban on legal highs, also known as new psychoactive substances (NPS) proposed by the Westminster government was not going to halt the spread.
Concerns about the substances include people not knowing what they contain, a lack of understanding about their effects and how strong they are.
Thaker Hafid, a father-of-three from Cardiff, died in February after taking a legal high that was five times stronger than heroin.
The project, being launched in Neath, Neath Port Talbot, will offer briefings across Wales with the aim of reaching more than 8,000 people by Christmas.
Public Health Wales has also warned about a potentially dangerous legal high currently in circulation.
A man was taken to hospital in north Wales on 15 June after taking MMB-CHMINACA (MDMD-CHMICA) which has been associated with six deaths across Europe since September 2014.

After mopping up Kent's first innings for 236 in the morning session, despite Sam Northeast racking up a century, Durham had a 212-run lead.
Graham Clark's career-best 83, helped by skipper Paul Collingwood's 51, saw Durham declare with a lead of 483.
Kent survived the final 10 overs of the day to end of 35 without loss.
Northeast had been the Kent hero on day two, with his unbeaten 109 aided by Yasir Shah's hard-earned 48 in a 113-run eighth-wicket partnership, before Durham hit back to reduce Kent from 236-8 to 236 all out.
South African opener Stephen Cook (44) continued his resurgence in Durham colours once he took to the crease, although partner Keaton Jennings was not so lucky as he departed for a first-ball duck.
Cameron Steel, who made 43, along with Clark and Collingwood put Jon Lewis' side in a decent position at the declaration, in spite of early exits for Ryan Pringle and Stuart Poynter.
Daniel Bell-Drummond and Sean Dickson nursed Kent to stumps without loss, but still trailing by 449 runs.

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5 August 2015 Last updated at 07:44 BST
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